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28 April 2025, Volume 29 Issue 12 Previous Issue    Next Issue

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Linagliptin alleviates wear particle-induced inflammatory osteolysis by regulating macrophage polarization and osteoclast formation Yang Peng, Zhang Wei, Li Wenming, Li Wenhao, Wu Zebin, Zhou Jun, Geng Dechun 2025, 29 (12):  2421-2428.  doi: 10.12307/2025.393 Abstract ( 183 )   PDF (2364KB) ( 150 )   Save BACKGROUND: Linagliptin exhibits the capacity to regulate macrophage polarization, shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators, thereby mitigating local inflammation.  OBJECTIVE: To explore the effects of linagliptin on macrophage polarization, osteoclast activation, and inflammatory osteolysis elicited by wear particles. METHODS: (1) Cell experiments: For macrophage polarization, RAW264.7 cells were cultured and divided into four groups: the control group received high-glucose culture medium; the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment; the low- and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin, respectively, for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction, immunofluorescence staining and RT-PCR were performed. For osteoclast activation, RAW264.7 cells were cultured and divided into four groups: the control group was cultured with high-glucose culture medium, the osteoclast-induced group and low- and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation, cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently, cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments: Twenty-four male C57BL/6J mice were randomly divided into four groups: sham operation group, model group, low-dose linagliptin group, and high-dose linagliptin group. The model group, low-dose linagliptin group, and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling, the low- and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg, respectively) once daily. After modeling for 3 weeks, serum macrophage polarization marker protein and inflammatory factor levels were detected; skull samples were collected for micro-CT scanning, bone parameter analysis, and hematoxylin-eosin staining to evaluate osteolysis and morphological changes. RESULTS AND CONCLUSION: (1) Cell experiments: Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P < 0.01). Notably, the high-dose group exhibited a more pronounced inhibitory effect (P < 0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P < 0.01), whereas inflammatory factor mRNA expression was significantly lower in the low- and high-dose linagliptin groups compared with the M1-induced group (P < 0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P < 0.01). Conversely, both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P < 0.01), with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments: Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption, with the high-dose group showing superior efficacy. To conclude, linagliptin has been shown to modulate macrophage polarization, inhibit osteoclast activation, and have a protective effect on the skeletal system.    中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Liquiritin inhibits osteoclast differentiation and alleviates bone loss  Zhang Wensheng, Guo Haiwei, Weng Rui, Mo Ling, Song Zhenjie, Tian Han, Zhong Yelin, Wang Yuancheng, Tang Hanwu, Liu Caijun, Yuan Chao, Li Ying 2025, 29 (12):  2429-2437.  doi: 10.12307/2025.383 Abstract ( 200 )   PDF (3423KB) ( 155 )   Save BACKGROUND: Relatively or absolutely active bone resorption function of osteoclasts is one of the causative factors of osteoporosis. Therefore, how to inhibit the formation of osteoclasts and reduce the bone resorption activity is a key element in the prevention and treatment of osteoporosis. Liquiritin, which is derived from licorice, plays a role in the clinical treatment of bone diseases, but there are fewer studies addressing the application of liquiritin in osteoporosis and the mechanism is unknown. OBJECTIVE: To confirm, through both in vivo and in vitro experiments, that liquiritin inhibits osteoclast differentiation and alleviates bone loss.  METHODS: Cell counting kit-8 was used to detect whether Liquiritin exerts toxic or proliferative effects on mouse bone marrow-derived macrophages, and tartrate-resistant acid phosphatase staining was performed to observe the effect of liquiritin in inhibiting osteoclast differentiation. The affinity of liquiritin binding to proteins related to osteoclast differentiation was verified by network pharmacology. RT-PCR and western blot assays were performed to detect the inhibitory effects of liquiritin on osteoclast-specific protein and gene expression as well as relevant signaling pathways. Finally, the mitigating effect of liquiritin on bone loss was verified in the C57BL/6J mouse osteoporosis model.  RESULTS AND CONCLUSION: Liquiritin, at concentrations of 20 μmol/L and below, could inhibit the formation and differentiation of osteoclasts. Concurrently, it exhibited a high affinity with osteoclast-specific proteins such as nuclear factor of activated T-cells 1, Cathepsin K, c-Fos, and matrix metalloproteinase 9, and reduced the relative expression levels of these genes and proteins. Liquiritin could also effectively lower the phosphorylation expression level of JNK in the MAPK signaling pathway at the 15th, 30th, 45th, and 60th minutes, and it could salvage the degradation of nuclear factor-κB inhibitor α in the nuclear factor-κB signaling pathway at the 60th minute. In vivo experiments demonstrated that liquiritin could mitigate bone loss caused by osteoclasts and improve parameters related to trabecular bone. To conclude, liquiritin possesses the capacity to inhibit osteoclast differentiation and alleviate bone loss, thereby exerting a protective role against osteoporosis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Alpinetin promotes fracture healing in rats with osteoporotic fracture by regulating the cAMP/PKA/CREB signaling pathway Lu Fei, Zhou Jing, Jin Tao 2025, 29 (12):  2438-2443.  doi: 10.12307/2025.371 Abstract ( 241 )   PDF (1943KB) ( 176 )   Save BACKGROUND: Alpinetin has anti-inflammatory, antitumor and antibacterial effects and has been proven to alleviate osteoporosis, but the effect and mechanism of alpinetin on osteoporotic fractures are still unclear. OBJECTIVE: To investigate the improvement effect of alpinetin in rates with osteoporotic fracture by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signaling pathway.  METHODS: A rat model of osteoporotic fracture was constructed using bilateral ovariectomy. The successfully modeled rats were randomly separated into model group, low-, medium-, and high-dose alpinetin group, and inhibitor group, with 12 rats per group. Another 12 rats were regarded as the sham operation group. On the day of fracture, rats in the low-, medium-, and high-dose alpinetin groups were gavaged with 7.5, 15, and 30 mg/kg alpinetin + intraperitoneally injected with an equal amount of normal saline, respectively; the inhibitor group was gavaged with 30 mg/kg alpinetin + intraperitoneally injected with 5 mg/kg  H-89 (a pathway inhibitor); and the model and sham operation groups were given (gavaged + intraperitoneally injected) an equal amount of normal saline, once a day for 8 consecutive weeks. Radiological examination was applied to evaluate fracture healing and assess healing scores; bone mineral density scanners were used to measure bone mineral density at the fracture site; three-point bending experiment and compression experiment were conducted to evaluate the biomechanical status of the femur; pathological damage at the fracture site in rats was observed by hematoxylin-eosin staining; enzyme linked immunosorbent assay (ELISA) was used to detect changes in serum alkaline phosphatase, osteocalcin, type I collagen cross-linked C-terminal peptide, and cAMP levels; western blot was applied to detect the expression of bone morphogenetic protein 2 and cAMP/PKA/CREB pathway proteins in femoral tissue.  RESULTS AND CONCLUSION: Compared with the sham operation group, the fracture healing score, bone mineral density, maximum load, maximum stress, alkaline phosphatase, osteocalcin, cAMP levels, bone morphogenetic protein 2, p-PKA/PKA, p-CREB/CREB expression in the model group were decreased, the level of type I collagen cross-linked C-terminal peptide was increased (P < 0.05). The above indicators showed opposite changes in all the alpinetin groups compared with the model group (P < 0.05). Compared with the high-dose alpinetin group, the changes in the above indicators were reversed in the inhibitor group (P < 0.05). To conclude, alpinetin may accelerate fracture healing in osteoporotic fracture rats, by activating the cAMP/PKA/CREB signaling pathway. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Constructing a Nomogram model of vulnerable carotid plaques in patients at high risk of stroke based on clinical baseline characteristics and carotid ultrasound parameters Qin Jie, Li Yujuan, Wang Bili, Lai Zefei, Ma Yueming 2025, 29 (12):  2444-2449.  doi: 10.12307/2025.386 Abstract ( 200 )   PDF (1741KB) ( 82 )   Save BACKGROUND: Studies have shown that the vulnerability and elasticity of carotid plaques are related to the presence and degree of neovascularization within the plaque. Ultrasound, as the preferred measure to screen and evaluate vulnerable carotid plaques, is non-invasive, easy to perform, highly reproducible and radiation-free. OBJECTIVE: To investigate the influencing factors of vulnerable carotid plaque in the high-risk stroke population based on clinical baseline characteristics and carotid ultrasound parameters, and to develop a Nomogram prediction model based on independent risk factors.  METHODS: A total of 180 patients who were identified to be at high risk of stroke by stroke screening at Fuzhou First People’s Hospital from November 2021 to November 2023 were retrospectively selected as the study objects, and the patients were divided into a modeling set (n=126) and a validation set (n=54) at a ratio of 7:3. According to the results of carotid artery ultrasound, the subjects in the modeling set were divided into a vulnerable plaque group (n=54) and a non-vulnerable plaque group (n=72). Independent risk factors were obtained by multi-factor Logistic regression, and a Nomogram model was constructed. Decision curves were drawn using R language to evaluate the clinical benefit of the model. The predictive efficacy of the model was tested by receiver operating characteristic curve and calibration curve, and the case data of the validation set were analyzed for external validation.  RESULTS AND CONCLUSION: Multivariate Logistic regression results showed that age, family history of stroke, maximum carotid plaque thickness, carotid plaque quantity, urine microalbumin, urine microalbumin/creatinine ratio were associated with vulnerable carotid plaques in patients at high risk of stroke (P < 0.05). The area under curve of the established Nomogram model was 0.917, and the sensitivity and specificity were 79.6% and 91.7%, respectively. The results of decision curve showed that the potential clinical benefit of this model was considerable and its usability was high. The calibration curve results showed that the model had good prediction accuracy. The verification set results showed that the external prediction performance of the model was good. To conclude, age, family history of stroke, and maximum carotid plaque thickness in the high-risk population are all factors that influence this prediction model. This Nomogram based on these independent risk factors can provide a powerful reference for the clinical treatment of this high-risk population. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Semen Ziziphi Spinosae extract regulates miR-7b-3p expression and promotes bone growth Luo Shiren, Wu Xiaolong, Xie Yan 2025, 29 (12):  2450-2457.  doi: 10.12307/2025.385 Abstract ( 213 )   PDF (1551KB) ( 133 )   Save BACKGROUND: Previous studies found that Semen Ziziphi Spinosae extract prolongs slow-wave sleep and promotes growth hormone secretion in mice by increasing the expression of brain tissue serotonin 1A receptor (5-HT1AR), which binds to serotonin, thus leading to bone growth. Serotonin 1A receptor acts as a protein, and its expression abundance is regulated by miRNAs. The authors hypothesized that Semen Ziziphi Spinosae extract may regulate the expression of 5-HT1AR through miRNAs and thus exert drug effects.  OBJECTIVE: To observe the effect of Semen Ziziphi Spinosae extract on bone growth by regulating the miR-7b-3p/5-HT1AR pathway in mouse brain tissue.  METHODS: (1) Kunming mice were divided into a normal control group, a drug administration group (gavage administration of Semen Ziziphi Spinosae extract 0.320 mg/g), a positive control group (gavage administration of jujuboside 0.013 mg/g), a Semen Ziziphi Spinosae extract+5-HT1AR selective inhibitor group  (8 μg of P-MPPF, a 5-HTIAR selective inhibitor, was injected into the lateral ventricle every day for the last 3 days during the gavage administration of Semen Ziziphi Spinosae extract). After 25 days, the effects of Semen Ziziphi Spinosae extract on bone growth, serum growth hormone level and brain 5-HT1AR expression were observed. (2) Then the chip method was used to observe differentially expressed miRNAs in the brain tissues of growing mice and ordinary mice. PCR validation and dual luciferase reporter gene assay confirmed the regulatory relationship between the screened Mir-7B-3p and 5-HT1AR. (3) Mouse cerebral cortical cells were cultured and identified in vitro, and the effect of Semen Ziziphi Spinosae extract on 5-HT1AR expression in cerebral cortical cells was observed using western blot. (4) Kunming mice were divided into a normal control group, a medication group, a miR-7b-3p inhibitor group, a medication +5-HT1AR inhibitor group, and a positive control group. The expression of 5-HT1AR in brain tissues of mice and the binding activity of 5-HT and 5-HT1AR were observed. (5) Sprague-Dawley rats were divided into a normal control group, a medication group, a miR-7b-3p inhibitor group, a medication+miR-7b-3p mimics group and a positive control group. Changes in slow wave sleep in mice were observed.  RESULTS AND CONCLUSION: (1) Semen Ziziphi Spinosae extract could promote the growth of body length and tibia, growth hormone secretion, and brain tissue 5-HT1AR level in mice. (2) The number of differentially expressed miRNAs screened by GeneChip was 16, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics results predicted that down-regulation of miR-7b-3p could regulate 5-HT1AR expression, and dual-luciferase reporter gene experiments confirmed a direct regulatory relationship between the two. (3) Semen Ziziphi Spinosae extract and silencing of miR-7b-3p expression in cerebral cortical cells could cause high expression of 5-HT1AR. After silencing of miR-7b-3p, 5-HT1AR expression, binding activity of serotonin and 5-HT1AR and growth hormone secretion in mouse brain tissue were all elevated. After overexpression of miR-7b-3p, 5-HT1AR expression, binding activity of serotonin and 5-HT1AR and growth hormone secretion were all reduced. Accordingly, the slow-wave sleep period in mice was also prolonged or shortened. To conclude, Semen Ziziphi Spinosae extract can reduce the level of miR-7b-3p and increase the expression of 5-HT1AR in brain tissue to prolong slow wave sleep and promote the secretion of growth hormone, thereby playing a postive effect on bone growth. These findings provide a scientific basis for the use of Semen Ziziphi Spinosae extract as a potential measure to promote bone growth.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Bioinformatics analysis and functional verification of hsa-miR-3202 in osteoarthritic chondrocytes Zhang Jiaqi, Liu Yanhong, Liang Huiting, Zhou Jingjing, Wang Yawen, Xu Jingyu, Li Yushuang, Lei Lijian, Hu Xiaoqin 2025, 29 (12):  2458-2465.  doi: 10.12307/2025.381 Abstract ( 193 )   PDF (2043KB) ( 161 )   Save BACKGROUND: The imbalance between proliferation and apoptosis of chondrocytes plays an important role in the occurrence and development of osteoarthritis. Previous studies have found that hsa-miR-3202 is involved in regulating the proliferation and apoptosis of various cells. However, no studies have explored the correlation between hsa-miR-3202 and osteoarthritis. OBJECTIVE: To investigate the expression of hsa-miR-3202 in osteoarthritic chondrocytes and its effect on the proliferation and apoptosis of chondrocytes. METHODS: (1) MicroRNAs differentially expressed in osteoarthritic chondrocytes were screened by biogenic analysis. Based on the current research situation at home and abroad, hsa-miR-3202 was selected for follow-up studies, and its target genes were predicted by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. (2) Human normal chondrocyte cell lines C28/I2 in logarithmic growth phase were selected and randomly divided into four groups for culture: in normal group, cells were cultured in normal medium for 24 hours, the medium was then changed to normal medium for another 6 hours of culture, and changed to normal medium for subsequent culture; in lipopolysaccharide group, cells were cultured in lipopolysaccharide-containing medium for 24 hours, the medium was then changed to normal medium for another 6 hours, and changed to normal medium for subsequent culture; in lipopolysaccharide+NC group, cells were cultured in lipopolysaccharide-containing medium for 24 hours, and then transfected with has-miR-3202 mimics control for 6 hours, and the medium was change to normal medium for subsequent culture; in lipopolysaccharide+hsa-miR-3202 mimics group, cells were cultured in lipopolysaccharide-containing medium for 24 hours and then transfected with has-miR-3202 mimics for 6 hours, and the medium was changed to normal medium for subsequent culture. After further 48 hours of culture, the expression level of hsa-miR-3202 was detected by fluorescence quantitative PCR and cell apoptosis was detected by flow cytometry. After further culture of 0-72 hours, cell proliferation activity was detected by cell counting kit-8. RESULTS AND CONCLUSION: Bioinformatics analysis results indicated that hsa-miR-3202 was significantly down-regulated in osteoarthritic chondrocytes. GO functional enrichment and KEGG pathway enrichment showed that the function of hsa-miR-3202 target gene was closely related to cell growth and apoptosis. The results of in vitro cell experiments showed that compared with the normal group, the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly decreased in the lipopolysaccharide group (P < 0.05), while the apoptotic rate was significantly increased (P < 0.05). Compared with the lipopolysaccharide group, the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly increased in the lipopolysaccharide+hsa-miR-3202 mimics group (P < 0.05), while the apoptotic rate was significantly decreased (P < 0.05). To conclude, the expression of hsa-miR-3202 is down-regulated in osteoarthritic chondrocytes to inhibit cell proliferation and promote cell apoptosis, thus affecting the occurrence and development of osteoarthritis.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Mechanism underlying microRNA-214 regulation of cartilage and subchondral bone metabolism in osteoarthritis Tian Sheng, Wang Xi, Wang Yongcheng, Liu Yaning, Yang Hongquan 2025, 29 (12):  2466-2474.  doi: 10.12307/2025.389 Abstract ( 164 )   PDF (1929KB) ( 149 )   Save BACKGROUND: The role of microRNA-214 in osteoporosis has been reported both at home and abroad, whereas the interrelationship between microRNA-214 and osteoarthritic articular cartilage and subchondral bone degeneration is unclear.  OBJECTIVE: To investigate the relationship between microRNA-214 and cartilage and subchondral bone degeneration in mice with knee osteoarthritis.  METHODS: Thirty C57BL/6J mice were randomly grouped: Experiment 1: sham operation group and medial meniscus destabilization group (n=3 per group) underwent hematoxylin-eosin staining and qPCR to detect changes in microRNA-214 gene expression; Experiment 2: sham operation group, medial meniscus destabilization group, medial meniscus destabilization+null-loaded adenovirus group (null-loaded group), and medial meniscus destabilization+microRNA-214 antagonist overexpression adenovirus group (antagonist group; n=6 per group). Cartilage tissues were taken from each group 4 weeks after surgery, and stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue. qPCR and western blot were used to detect the expression of related factors in articular cartilage. RESULTS AND CONCLUSION: (1) In Experiment 1, hematoxylin-eosin staining results showed that cartilage degeneration was visible in the medial meniscus destabilization group compared with the sham operation group. qPCR assay results showed that microRNA-214 was expressed in all the samples, and the expression level of microRNA-214 in cartilage samples of the medial meniscus destabilization group was significantly higher than that of the sham operation group (P < 0.05). (2) In Experiment 2, the results of hematoxylin-eosin staining, safranin O-fast green staining, and toluidine blue staining showed that the degree of cartilage degeneration in the antagonist group was significantly reduced compared with the medial meniscus destabilization group. Adenovirus-validated PCR assay showed that the microRNA-214 expression level in cartilage tissue was higher in the null-loaded group than in the antagonist group (P < 0.05). (3) In Experiment 2, X-ray results showed typical osteoarthritis imaging changes in the medial meniscus destabilization group and null-loaded group, while the degree of degenerative joint lesions was relatively mild in the antagonist group. The results of microcomputed tomography showed that after injection of microRNA-214 antagonist, trabecular structure model index became smaller in the antagonist group, and the data were better than those of the medial meniscus destabilization group and null-loaded group. (4) In Experiment 2, western blot results showed that The relative expression levels of cartilage-associated factor type II collagen α1, sex-determining region Y-box 9, Runt-associated transcription factor 2, and osteopontin in cartilage specimens of the medial meniscus destabilization group and the null-loaded group were lower than that in the sham operation group and the antagonist group (P < 0.05), whereas the relative expression level of matrix metalloproteinase 13 was higher in the medial meniscus destabilization group and the null-loaded group than the sham operation group and the antagonist group (P < 0.05). (5) In Experiment 2, PCR results indicated that the relative mRNA expression of tumor necrosis factor-α and interleukin-6 was relatively higher in the medial meniscus destabilization group and null-loaded group, but relatively lower in the antagonist group, as compared with the sham operation group (P < 0.05). The relative mRNA expression of tumor necrosis factor-α and interleukin-6 was also higher in the medial meniscus destabilization group and the null-loaded group compared with the antagonist group (P < 0.05). To conclude, the expression level of microRNA-214 in articular cartilage was elevated in the mouse osteoarthritis model, suggesting that the elevated expression level of microRNA-214 is closely related to osteoarthritis; and injection of microRNA-214 antagonist into the knee joint cavity of the mouse osteoarthritis model could delay articular cartilage degradation, promote subchondral bone remodeling, and ameliorate the progression of osteoarthritis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Moxibustion alleviates cartilage lesions in rats with knee osteoarthritis through regulating the circPan3/miR-667-5p/Ghrelin signaling pathway Liao Qing, Zeng Jing, Chen Jun, Yuan Lixia, Liu Gang 2025, 29 (12):  2475-2483.  doi: 10.12307/2025.394 Abstract ( 190 )   PDF (2765KB) ( 126 )   Save BACKGROUND: Previous studies have demonstrated that moxibustion can alleviate osteoarthritis-induced cartilage lesions and delay the progression of knee osteoarthritis. In a previous study conducted by our research group, it was found that regulating the circPan3/miR-667-5p/Ghrelin signaling pathway can enhance the level of autophagy in chondrocytes, thereby exerting a cartilage protective role in knee osteoarthritis.  OBJECTIVE: To explore the effect of moxibustion on knee osteoarthritis cartilage in rats based on the circPan3/miR-667-5p/Ghrelin signaling pathway.  METHODS: Sprague-Dawley rats were randomly divided into three groups (n=10 per group): sham operation, model, and moxibustion groups. A rat model of knee osteoarthritis was established in the latter two groups by anterior cruciate ligament transection and medial meniscus resection. Rats in the sham operation group underwent arthrotomy only. At 6 weeks after modeling, moxibustion intervention at Zusanli and Shenyu acupoints was applied in the moxibustion group, 20 minutes daily for 4 weeks, while the other two groups did not receive any special treatment. After 4 weeks, histopathological staining was performed to observe the degree of synovial lesions and cartilage damage in the knee joint. Additionally, changes in the serum levels of inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, were detected by enzyme-linked immunosorbent assay. Furthermore, chondrocytes isolated from the above three groups of rats were divided into three groups: a normal control group, a model group, and a moxibustion group. The expression levels of cartilage matrix anabolic molecules (type II collagen and Sox9), matrix degradation molecules (matrix metalloproteinase 13 and ADAMTS5), autophagy markers (ATG5, Beclin-1, microtubule-associated protein 1 light chain 3), Ghrelin, CircPan3, and miR-667-5P were determined by western blot and qRT-PCR in each group. RESULTS AND CONCLUSION: After 4 weeks of treatment, the model group exhibited significant thickening of the synovium, infiltration of inflammatory cells, narrowing of the joint space, rough and uneven cartilage surfaces, thinning, reduction in the number of chondrocytes, a significant increase in synovitis and Osteoarthritis Research Society International scores, and a significant up-regulation of interleukin-6 and tumor necrosis factor-α levels (P < 0.000 1). In comparison, the sham operation group showed no significant changes. Compared with the model group, the moxibustion group exhibited a reduction in synovial thickening, a decrease in inflammatory cell infiltration, an increase in joint space, a reduction in cartilage roughness and loss of integrity, an increase in the number of chondrocytes, a reduction in synovitis and Osteoarthritis Research Society International scores, and a significant reduction in the levels of interleukin-6 and tumor necrosis factor-α (P < 0.000 1). The results of in vitro experiments demonstrated that the expression of matrix metalloproteinase 13, ADAMTS5, and miR-667-5P was elevated, while the expression of type II collagen, Sox9, autophagy markers, Ghrelin, and Circpan3 was reduced in the model group compared with the normal control group (P < 0.01). Moxibustion was found to reverse these changes in the moxibustion group compared with the model group (P < 0.01). To conclude, moxibustion may enhance chondrocyte autophagy by modulating the circPan3/miR-667-5p/Ghrelin signaling pathway, which may inhibit knee osteoarthritis inflammation and cartilage destruction, exerting a protective effect on cartilage. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Mechanism underlying the effect of formononetin on interleukin-1beta-induced chondrocyte injury #br# #br# Shan Jixin, Ye Ruibin, Ju Shaohua, Wang Qiang 2025, 29 (12):  2484-2491.  doi: 10.12307/2025.388 Abstract ( 200 )   PDF (2115KB) ( 30 )   Save BACKGROUND: Formononetin is an isoflavonoid compound widely found in red clover, astragalus, and chickweed, which has the ability to inhibit oxidative stress, inflammatory factor release, and apoptosis.  OBJECTIVE: To investigate the effect of formononetin on interleukin-1β-induced chondrocyte injury and its mechanism.  METHODS: (1) Cartilage tissues from patients with osteoarthritis and patients with simple meniscus injury were collected, and real-time quantitative PCR was used to detect miR-135b-5p expression. (2) Human chondrocytes were cultured in vitro, and then divided them into nine groups: cells in normal control group were cultured for 48 hours with no treatment; cells in interleukin-1β group were treated with interleukin-1β for 48 hours; cells in interleukin-1β+low-dose formononetin group were treated with 25 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours; cells in interleukin-1β+middle-dose formononetin group were treated with 50 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours; cells in interleukin-1β+high-dose formononetin group were treated with 100 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours; cells in interleukin-1β+miR NC group were treated with miR NC for 6 hours followed by treatment with interleukin-1β for 48 hours; cells in interleukin-1β+miR-135b-5p group were treated with miR-135b-5p mimics for 6 hours followed by treatment with interleukin-1β for 48 hours; cells in interleukin-1β+high-dose formononetin+anti-miR-NC group were treated with anti-miR-NC for 6 hours, then treated with 100 μmol/L formononetin for 24 hours, and finally treated with interleukin-1β for 48 hours; cells in interleukin-1β+high-dose formononetin+anti-miR-135b-5p group were treated with anti-miR-135b-5p for 6 hours, then treated with 100 μmol/L formononetin for 24 hours, and finally treated with interleukin-1β for 48 hours. Relevant tests are performed after treatment. RESULTS AND CONCLUSION: The expression level of miR-135b-5p in cartilage tissue of patients with osteoarthritis was significantly lower than that of patients with simple meniscus injury (P < 0.05). Compared with the normal control group, the expression level of miR-135b-5p, proliferative ability, activity of superoxide dismutase, and expression levels of collagenase II protein and Bcl-2 protein in chondrocytes were lower in the interleukin-1β group (P < 0.05), while apoptotic rate, lactate dehydrogenase activity, malondialdehyde level, levels of proinflammatory factors, and expression levels of matrix metalloproteinase-13 protein and Bax protein were higher in the interleukin-1β group (P < 0.05). Formononetin inhibited chondrocyte damage caused by interleukin-1β in a concentration-dependent manner. Transfection of miR-135b-5p mimics elevated miR-135b-5p expression in the interleukin-1β group and inhibited chondrocyte damage induced by interleukin-1β; transfection of anti-miR-135b-5p decreased miR-135b-5p expression in the interleukin-1β+high-dose formononetin group and inhibited the effect of formononetin on chondrocytes. To conclude, the protective effect of formononetin on chondrocyte injury induced by interleukin-1β may be related to the regulation of miR-135b-5p expression. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Role and mechanism of long non-coding RNA HSFAS in hypertrophic scar analyzed using RNA pull-down combined mass spectrometry  Xia Tongtong, Ma Fang, Sun Haoyuan, Liu Honglin, Zhang Zhenghao, Yang Jiaqi, Zhang Huiping, Wu Kai, Shen Jiangyong, Jiang Yideng, Li Guizhong 2025, 29 (12):  2492-2499.  doi: 10.12307/2025.382 Abstract ( 227 )   PDF (3217KB) ( 426 )   Save BACKGROUND: Previous studies found that the proliferative scar-specific long non-coding RNA lncRNA HSFAS is a novel biomarker that can be used in the diagnosis of hypertrophic scar, but how it functions in hypertrophic scar is not clear. OBJECTIVE: To investigate the role and mechanism of lncRNA HSFAS in hypertrophic scar.  METHODS: Fresh scar tissue and surrounding normal skin tissue samples from three patients with hypertrophic scar were collected, and tissue immunofluorescence was used to detect the expression of lncRNA HSFAS in frozen sections of two skin tissues. Primary fibroblasts were isolated from proliferative scarred skin tissue and normal skin tissue and cultured by enzyme digestion method. Quantitative real-time PCR was used to detect the mRNA expression of lncRNA HSFAS in cells. The proteins bound to lncRNA HSFAS were detected by RNA pull-down combined mass spectrometry. GO and KEGG were used to analyze the main functions and pathways of lncRNA HSFAS involved in hypertrophic scar progression. The targeted binding of lncRNA HSFAS to proteins was determined by catRAPID and RPISeq website analysis.  RESULTS AND CONCLUSION: Compared with normal skin tissue and fibroblasts from normal skin tissue, the expression of lncRNA HSFAS in human hypertrophic scar tissue and primary fibroblasts from hypertrophic scar tissue was significantly increased (P < 0.05). There were 510 proteins clearly bound to lncRNA HSFAS by RNA pull-down combined mass spectrometry. The results of GO and KEGG analyses showed that these proteins were mainly involved in RNA splicing and processing, chromosome synthesis and separation, and cell cycle. Among them, the proteins involved in RNA splicing and processing included scaffold attachment factor B2 and DICER1, and the binding fraction with lncRNA HSFAS was higher. The results of bioinformatics analysis showed that lncRNA HSFAS was bound to scaffold attachment factor B2 and DICER1 proteins. To conclude, lncRNA HSFAS may affect gene expression by interacting with scaffold attachment factor B2 and DICER1 proteins to regulate RNA splicing and processing modification, thus promoting the occurrence and development of hypertrophic scar. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Expression and regulation of miR-192-5p in hypertrophic scar tissue and fibroblasts Zhao Jiaojun, Tian Wengrong, Bu Panpan, Qi Yusong, Ma Zhiwei, Li Peipei, Ma Shaolin 2025, 29 (12):  2500-2506.  doi: 10.12307/2025.247 Abstract ( 169 )   PDF (1465KB) ( 168 )   Save BACKGROUND: miRNAs expression has been reported to be associated with hepatic and renal fibrosis, and dermal fibrogenesis. Moreover, a targeted regulatory relationship between miR-192-5p and epidermal regulators has been demonstrated in gouty arthritis. OBJECTIVE: To investigate the expression and regulatory role of miR-192-5p in hypertrophic scar and to verify whether there is a targeted regulatory relationship between miR-192-5p and epidermal regulators. METHODS: (1) Six cases of hypertrophic scar tissue and six cases of normal skin tissue were collected from the First Affiliated Hospital of Xinjiang Medical University. And miR-192-5p and epidermal regulator mRNA expression were detected by qRT-PCR. (2) The primary hypertrophic scar fibroblasts were obtained using tissue explant method and cultured to 3-6 generations for subsequent experiments. There were three groups in the experiment: negative control group, miR-192-5p mimic group and miR-192-5p inhibitor group. The latter two groups were transfected with the corresponding sequences. Cell proliferation viability was detected by the cell counting kit-8 assay and EdU kit; and the migration ability was detected by the cell scratch test. Cell apoptosis was detected by flow cytometry. The gene and protein expressions of epidermal regulator, type I collagen, type III collagen and α-smooth muscle actin were detected by qRT-PCR and western blot, respectively. miR-192-5p targets were predicted by a bioinformatics website, and target binding was validated by dual luciferase assay.  RESULTS AND CONCLUSION: (1) Compared with normal skin tissues and their fibroblasts, miR-192-5p and epidermal regulator were highly expressed in hypertrophic scar and hypertrophic scar fibroblasts (P < 0.05 or P < 0.01). (2) After overexpression of miR-192-5p, cell proliferation was enhanced (P < 0.05) and EdU positive cell rate increased (P < 0.01) when compared with the negative control group; after inhibition of miR-192-5p, cell viability (P < 0.05) and EdU positive rate decreased (P < 0.05). (3) At 24 hours after overexpression of miR-192-5p, compared with the negative control group, the area between cell scratches and apoptosis rate decreased in the miR-192-5p mimic group (P < 0.05) but increased in the miR-192-5p inhibitor group (P < 0.01). (4) At 48 hours after transfection, the mRNA and protein levels of epidermal regulator were significantly decreased in the miR-192-5p mimic group, while the mRNA and protein levels of type I collagen, type III collagen and α-smooth muscle actin were significantly increased (P < 0.05 or P < 0.01). The miR-192-5p inhibitor group showed opposite changes in the above four indicators (P < 0.05 or P < 0.01). (5) The Targetscan website predicted that epidermal regulator had a potential binding site for miR-192-5p. (6) Dual luciferase assays showed that miR-192-5p could bind to epidermal regulator in a targeted manner. To conclude, overexpression of miR-192-5p can decrease the expression of epidermal regulator, and the two may be negatively regulated, suggesting that regulation of epidermal regulator may play a role in inhibiting the proliferation of hypertrophic scar fibroblasts. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Application of stamp-shaped skin allograft in extremely severe burns following failure of Meek skin grafting Tian Chenyang, Tao Ke, Ji Peng, Wang Yunchuan, Hu Dahai, Gao Xiaowen, Zheng Zhao 2025, 29 (12):  2507-2512.  doi: 10.12307/2025.390 Abstract ( 171 )   PDF (1216KB) ( 152 )   Save BACKGROUND: Postoperative results with Meek skin grafting in some patients with extremely severe burns have not been satisfactory, with problems of delayed healing or skin graft failure. There have been fewer studies on the treatment of patients with failed Meek skin grafting due to insufficient skin source. This study aimed to explore a treatment method for such patients. OBJECTIVE: To observe the curative effect of stamp-shaped skin allograft in the treatment of severe burns after Meek skin graft failure.  METHODS: Twenty-three patients with extremely severe burns who were admitted at Department of Burns and Skin Surgery, the First Affiliated Hospital of the Air Force Medical University from August 2013 to August 2023 with poor healing after Meek skin grafting were enrolled and divided into allogeneic skin treatment group and dressing change group according to different treatment methods. There were 10 cases in the allograft group and 13 cases in the dressing change group. Preoperative hemoglobin, platelet count, albumin count, white blood cell count, neutrophil count, procalcitonin count, and positive rate of microbial culture before secondary Meek skin grafting were compared between two groups. Survival rate of skin grafts before and after the second operation were compared. The number of operations, incidence of sepsis, and wound scars at 3 months and 6 months after operation were retrospectively analyzed.  RESULTS AND CONCLUSION: The preoperative hemoglobin, platelet count and albumin count in the allogeneic skin treatment group were significantly higher than those in the dressing change group (Z=-3.172, P=0.002; Z=-3.010, P=0.003; Z=-2.761, P=0.006). There was no significant difference in the preoperative white blood cell count and neutrophil count between the two groups before secondary Meek skin grafting (Z=1.148, P=0.251; Z=0.373, P=0.709), but the serum procalcitonin count in the allogeneic skin treatment group prior to the second operation was significantly lower than that in the dressing change group (Z=2.955, P=0.002). Burn patients in the dressing change group exhibited a higher microbial culture rate than those in the allogeneic skin treatment group (χ²=6.303, P=0.029). The survival rate of skin grafts before the second operation in the allogeneic skin treatment group [(74.8±13.3)%] was significantly higher than that in the dressing change group [(58.4±14.2)%; t=2.85, P=0.01). The survival rate of skin grafts after the second stage operation in the allogeneic skin treatment group [(84.0±11.5)%] was significantly higher than that in the dressing change group [(67.6±20.7)%; t=2.24, P=0.03). The frequency of postoperative surgery in the allogeneic skin treatment group was less than that in the dressing change group (Z=2.27, P=0.02). The incidence of sepsis in the dressing change group was significantly higher than that in the allogeneic skin treatment group (χ²=5.490, P=0.03). There was no significant difference in the Vancouver Scar Scale scores of the scars between the two groups at 3 and 6 months after operation (t=0.96, 1.138, P > 0.05). To conclude, stamp-shaped skin allograft has good curative effect in the treatment of wounds with poor healing of skin after Meek micro-transplantation. The utilization rate of skin in the later stage is significantly increased, which reduces the probability of wound infection and solves the problem of insufficient skin source.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Topological characteristics of muscle functional networks during repeated leg press to exhaustion Zhang Chen, Ran Linghua, Hu Huimin, Zhang Xin, Zhou Zijian, Xu Hongqi, Shi Jipeng 2025, 29 (12):  2513-2520.  doi: 10.12307/2025.392 Abstract ( 184 )   PDF (1562KB) ( 128 )   Save BACKGROUND: Surface electromyography has been extensively utilized for monitoring muscle fatigue. However, traditional electromyographic metrics typically focus on individual muscles and fail to assess the variations in a muscle group during the fatigue process. OBJECTIVE: To establish a muscle functional network to extract complex network parameters and investigate the topological property changes of the muscle functional network under different levels of fatigue, aiming to provide theoretical and methodological foundations for fatigue monitoring and prevention.  METHODS: Eleven participants performed single-leg leg press exercise at 50% of one-repetition maximum until exhaustion. Simultaneously, electromyographic signals of seven muscles (rectus femoris, vastus lateralis, vastus medialis, biceps femoris, tibialis anterior, lateral gastrocnemius, and medial gastrocnemius), electrocardiographic signals, and Borg CR-10 scale scores were collected. The Borg CR-10 scale was used to categorize three fatigue stages: mild, moderate, and severe. Heart rate and heart rate variability were calculated to validate the effective division of fatigue stages. Using the coherence of muscle signals, a muscle functional network was constructed with the seven muscles as nodes, and four complex network parameters (clustering coefficient, average weighted degree, global efficiency, and eigenvector centrality) were extracted. Additionally, four electromyographic indices (root mean square, median frequency, instantaneous mean frequency, and co-activation ratio) were extracted and compared under the three levels of fatigue.  RESULTS AND CONCLUSION: (1) Differences in heart rate and heart rate variability were observed across three fatigue stages, indicating the effectiveness of fatigue stage delineation. (2) Electromyographic indicators for different muscles under three levels of fatigue: root mean square and co-activation ratio showed no differences; however, median frequency exhibited robust fatigue trends in vastus lateralis, vastus medialis, and biceps femoris, while instantaneous mean frequency demonstrated robust fatigue trends in rectus femoris, vastus lateralis, vastus medialis, and biceps femoris. Instantaneous mean frequency outperformed median frequency and root mean square, yet all three indicators showed robust trends only for the major working muscle groups, unaffected by fatigue factors, unlike the co-activation ratio. (3) The connectivity strength between vastus lateralis and vastus medialis, vastus lateralis and biceps femoris, vastus lateralis and gastrocnemius medialis, and vastus medialis and biceps femoris gradually increased, showing significant differences in average weighted degree, clustering coefficient, and global efficiency post-fatigue, significantly correlated with fatigue levels. To conclude, changes in connectivity strength reflect the synergy and complementarity among muscles during fatigue. Clustering coefficient, average weighted degree, and global efficiency serve as fatigue markers reflecting overall muscle changes. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effects of 12 weeks of low-intensity resistance training combined with blood flow restriction training on body composition, muscle strength, and arterial elastic function in young adults Jia Yuexin, Tian Saisai, Qi Xiaohong, Zhang Suqin 2025, 29 (12):  2521-2527.  doi: 10.12307/2025.395 Abstract ( 222 )   PDF (1133KB) ( 141 )   Save BACKGROUND: High-intensity resistance training effectively improves muscle strength, but with a high risk of arteriosclerosis; high-intensity resistance training combined with aerobic exercise effectively reduces the level of arteriosclerosis; low-intensity resistance combined with blood flow restriction training does not require high load strength to stimulate muscles, which may be a scientific training method to improve muscle strength and maintain arterial elasticity. OBJECTIVE: To explore the effects of 12 weeks of low-intensity resistance training combined with blood flow restriction training on body composition, muscle strength, and arterial elasticity in young people, thereby providing theoretical support for the development of personalized training programs. METHODS: Fifty-five college students were randomly recruited and divided by drawing lots into high-intensity resistance training group, high-intensity resistance training combined with aerobic exercise group, and low-intensity resistance training combined with blood flow restriction training group. All participants were subjected to 12 weeks of high-intensity resistance training, high-intensity resistance training combined with aerobic exercise, or low-intensity resistance training combined with blood flow restriction training, and their body composition, muscle strength, and arterial elasticity were tested after training.  RESULTS AND CONCLUSION: After 12 weeks of training intervention, the lean body mass of the high-intensity resistance training group and the low-intensity resistance training combined with blood flow restriction training group significantly increased (P < 0.05). The one-repetition maximum and knee isokinetic muscle strength significantly increased in all the three groups (P < 0.05). The arterial elasticity of the high-intensity resistance training combined with aerobic exercise group and the low-intensity resistance training combined with blood flow restriction training group significantly improved (P < 0.05). These findings indicate that 12 weeks of high-intensity resistance training and low-intensity resistance training combined with blood flow restriction training significantly improve body composition; all the three training programs can increase muscle strength; 12 weeks of high-intensity resistance training combined with aerobic exercise and low-intensity resistance training combined with blood flow restriction training both improve arterial elasticity, and the effect of low-intensity resistance training combined with blood flow restriction training is superior to that of high-intensity resistance training combined with aerobic exercise. Therefore, it is recommended that low-intensity resistance training combined with blood flow restriction training be used as the preferred training method to improve arterial elasticity, thus reducing the risk of arteriosclerosis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Extraction and characterization of three types of primary cells from rat intervertebral disc and their matrix expression in monolayer and micromass culture Hu Siyuan, Chen Jianquan 2025, 29 (12):  2528-2535.  doi: 10.12307/2025.362 Abstract ( 218 )   PDF (1680KB) ( 157 )   Save BACKGROUND: Currently, methods for obtaining primary intervertebral disc cells are mostly cumbersome and there is a lack of relevant reports on the simultaneous extraction of three types of cells. Therefore, it is crucial to find a method to simultaneously extract three types of cells. OBJECTIVE: To explore a method for simultaneously extracting and culturing three types of intervertebral disc cells from rats, to identify them, and to investigate the effects of monolayer versus micromass cultures on the extracellular matrix. METHODS: The cartilaginous endplate (CEP), nucleus pulposus (NP), and annulus fibrosus (AF) tissues were separated from 3-week-old male Sprague-Dawley rat intervertebral disc tissue. For the nucleus pulposus and annulus fibrosus tissues, 0.1% pronase E was used for 30 minutes of digestion at 37 °C followed by 0.2% collagenase type II digestion for 4 hours to release the cells; for the cartilaginous endplate tissue, direct digestion with 0.2% collagenase type II for 4 hours was performed to release the cells. The cells, after removal of the digestion enzymes, were seeded into culture dishes containing culture medium, and their morphology was observed. Real-time fluorescence quantitative PCR and western blot assay were performed to detect the expression levels of various cell markers. Rat primary annulus fibrosus cells and cartilaginous endplate cells were cultured in monolayer or micromass cultures, and Alcian blue and Safranin O staining were used to assess the extracellular matrix expression capability. RESULTS AND CONCLUSION: After 4 days of culture, all three types of intervertebral disc cells began to adhere to the bottom of the dish and gradually showed proliferative vitality. By the 8th day of culture, significant proliferation of the three types of cells was observed, with a spindle-shaped morphology. Notably, the nucleus pulposus cells exhibited multivesicular notochord-like cells. Through real-time fluorescence quantitative PCR and/or western blot assay, it was found that primary nucleus pulposus cells highly expressed Cytokeratin 19 (K19) and Carbonic anhydrase 3 (Car3), primary annulus fibrosus cells highly expressed Secreted protein acidic and cysteine rich (Sparc) and Biglycan (Bgn), and primary cartilaginous endplate cells highly expressed Parathyroid hormone receptor 1 (Pth1r) and Leucyl-tRNA synthetase 2 (Lars2). After micromass culture of primary annulus fibrosus and cartilaginous endplate cells, Alcian blue and Safranin O staining demonstrated that this culture method could enhance the expression capability of the extracellular matrix compared with monolayer culture. These results indicate that primary intervertebral disc cells extracted and cultured by this method have a good morphology and a high level of extracellular matrix expression. This method holds promise as a research tool to aid researchers in understanding the biology of intervertebral discs. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Anti-obesity effect of insulin-like growth factor 1 in naturally aging mice Zhu Peng, Li Yingyu, Lu Xiaoqian, Wu Qiong 2025, 29 (12):  2536-2543.  doi: 10.12307/2025.324 Abstract ( 177 )   PDF (1953KB) ( 66 )   Save BACKGROUND: In our previous experiments, it was found that transplantation of young adipose stem cells into aged mice would have weight loss effect and improve the inflammatory state in aged mice. Therefore, we speculate that insulin-like growth factor 1 may play an important role in aging and obesity. OBJECTIVE: To explore the anti-obesity effect of insulin-like growth factor 1 in naturally aging mice. METHODS: (1) Bioinformatics analysis: Sequencing of adipose tissue from obese patients in the GEO database and transcriptomic sequencing of young mouse adipose stem cells and old adipose stem cells were conducted to analyze insulin-like growth factor 1 expression. (2) Animal experiment verification: Six young C57BL/6J mice and twelve aged C57BL/6J mice (20 months old) were selected. Abdominal adipose tissue and serum insulin-like growth factor 1 expression in young and aged mice were examined by ELISA and qRT-PCR. All the 12 aged mice were randomly divided into two groups with 6 mice in each group: the experimental group was given insulin-like growth factor 1 (50 μg/kg) for 4 continuous weeks, while the control group was given the same amount of phosphate buffer saline. The body mass changes of mice were monitored regularly, glucose tolerance was measured at the end of the experiment, and serum inflammatory factors and inflammatory factors in abdominal white adipose tissue of mice were detected by ELISA. Hematoxylin-eosin staining was used to observe pathological changes in the mouse liver, kidney and abdominal white adipose tissue. The mRNA expression levels of inflammatory factors and PI3K-Akt signaling pathway in abdominal white adipose tissue of mice were detected by qRT-PCR. RESULTS AND CONCLUSION: Obese patients showed lowly expressed insulin-like growth factor 1 in adipose tissue, but the expression of insulin-like growth factor 1 increased after weight loss surgery. Insulin-like growth factor 1 expressed lowly in aged adipose stem cells. Insulin-like growth factor 1 also showed a low expression in adipose tissue and serum of aged mice. Injection of insulin-like growth factor 1 protein could significantly reduce the body mass of aged mice and improve insulin resistance. Pathological sections of the liver of aged mice revealed fat accumulation. After injection of insulin-like growth factor 1 protein, fat accumulation was significantly improved and the size of fat droplets in adipose tissue was significantly reduced. Insulin-like growth factor 1 injection significantly reduced the expression levels of serum tumor necrosis factor α, interleukin 1β, and interleukin 6 in aged mice, and significantly increased the expression of PI3K-AKT signaling pathway in adipose tissue of aged mice. To conclude, exogenous insulin-like growth factor 1 can reduce body mass, reduce fat droplet size in adipose tissue, and improve liver fat accumulation in aged mice, thereby improving their inflammatory status. Exogenous insulin-like growth factor 1 may activate the PI3K-AKT signaling pathway to improve the inflammatory symptoms in aged mice, thereby improving obesity in naturally aging mice. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effect of transcranial magnetic stimulation on potassium channels in the dentate gyrus of the hippocampus of Alzheimer’s disease mice Qian Lei, Yu Hongli, Zhao Xiuzhi, Zhu Yucan 2025, 29 (12):  2544-2552.  doi: 10.12307/2025.379 Abstract ( 177 )   PDF (2005KB) ( 136 )   Save BACKGROUND: Transcranial magnetic stimulation has been used in the treatment of Alzheimer’s disease, but its mechanism has not been fully clarified. OBJECTIVE: To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer’s disease. METHODS: Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation, 2 hours daily, for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer’s disease on action potentials; and the potassium channel currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION: The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation, while Alzheimer’s disease led to a decrease in the learning and memory ability of mice, a decrease in the number of times they found the platform, and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer’s disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer’s disease mice. Analysis of potassium channel currents showed that Alzheimer’s disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged, causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions, which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude, repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Blood flow restriction training in the prevention and rehabilitation of foot and ankle injuries Zhang Dakuan, Li Yongjie, Han Libao, Liu Hongju, Liu Mengling, Fu Shenyu 2025, 29 (12):  2553-2559.  doi: 10.12307/2025.377 Abstract ( 252 )   PDF (1117KB) ( 303 )   Save BACKGROUND: In recent years, the use of blood flow restriction training in the rehabilitation of ankle injuries has gradually increased, and this technique can improve muscle strength, and can achieve a similar effect of high-load resistance training when combined with low-intensity resistance training. OBJECTIVE: To elucidate the current application status of blood flow restriction training in the prevention and rehabilitation of foot and ankle injuries. METHODS: A literature search was conducted on CNKI, PubMed, and Web of Science databases. The Chinese search terms were “blood flow restriction training, pressure training, ankle, ankle joint,” and the English search terms were “blood flow restriction, BFR, KAATSU, ankle, foot.” Relevant literature from database inception to July 2023 was retrieved, and 50 articles were ultimately included according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: In foot and ankle applications, blood flow restriction training is primarily used in studies of Achilles tendon thickness and ankle muscle strength in healthy individuals, as well as in chronic ankle instability, after Achilles tendon ruptures, and after external ankle fractures. Single blood flow restriction training can reduce the thickness of Achilles tendon in healthy individuals, while long-term training can make it thicker. Blood flow restriction training can prevent muscle strength decline in healthy individuals, while low-intensity blood flow training can promote ankle muscle strength recovery in injured patients. In current research, few adverse events related to blood flow restriction have been found, and future research should compare the efficacy of different training programs in different populations and optimize the research content. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Natural products regulate oxidative stress in the treatment of spinal cord injury Zhang Xiaowei, Yan Binghan, Qiu Daodi, Xue Haipeng, Tan Guoqing, Xu Zhanwang 2025, 29 (12):  2560-2568.  doi: 10.12307/2025.378 Abstract ( 254 )   PDF (1233KB) ( 191 )   Save BACKGROUND: Spinal cord injury is a serious neurological disease that often results in severe neurological impairment. Oxidative stress is an important link in the pathological process after spinal cord injury, leading to neuronal cell death and loss of function. In recent years, natural products have shown potential application values in the treatment of oxidative stress after spinal cord injury due to their wide range of sources, diverse structures and rich biological activities.  OBJECTIVE: To discuss the therapeutic effects of some natural products on oxidative stress after spinal cord injury and the related mechanisms, in order to provide new ideas and directions for antioxidant therapy of spinal cord injury.  METHODS: “Spinal cord injury, oxidative stress, anti-oxidation, natural products, natural compounds, polyphenols” were used as the English and Chinese keywords in PubMed, Web of Science, Embase, Cochrane, VIP, CBM, WanFang, and CNKI databases to search relevant articles published from database inception to May 2024. Inclusion and exclusion criteria were developed, and 97 relevant articles were selected by reading titles, abstracts, and full texts.  RESULTS AND CONCLUSION: Natural products such as polyphenols can directly scavenge oxidative free radicals by the phenol hydroxyl group in their structure, and alleviate oxidative stress after spinal cord injury. Some natural products can enhance the activity of relevant antioxidant enzymes in vivo and reduce oxidative stress by regulating certain signal transduction pathways. Some natural products can reduce oxidative stress after spinal cord injury by enhancing autophagy. The use of natural products to regulate oxidative stress may become an effective tool for the future clinical treatment of spinal cord injury. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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The molecular mechanism of necroptosis and its correlation with periodontitis Sun Huanhuan, Zhao Fei, Tao Ran, Liu Bing 2025, 29 (12):  2569-2574.  doi: 10.12307/2025.370 Abstract ( 215 )   PDF (1031KB) ( 230 )   Save BACKGROUND: In recent years, with the deepening of cell death research, necroptosis has gradually become a hot and difficult topic in academic research.  Its various signaling pathways and proteins play an important role in the occurrence and development of periodontitis. People try to delay the process of periodontal tissue inflammation by preventing the occurrence of necroptosis. OBJECTIVE: To provide a review on the molecular mechanism of necroptosis and its correlation with periodontitis in the hope of providing new ideas and directions for the prevention, diagnosis, treatment and evaluation of periodontitis. METHODS: The first author searched PubMed, CNKI, and other databases in October 2023 for relevant literature published up to April 2024 with the search terms of “necroptosis, programmed cell death, periodontitis, periodontal, immunity, inflammation, receptor interacting protein kinase 1, receptor interacting protein kinase 3, mixed lineage kinase domain-like” in Chinese and “necroptosis, programmed cell death, periodontitis, periodontal, immunity, inflammation, RIP1, RIP3, MLKL” in English, respectively. The titles and abstracts of each document were read for preliminary screening, and 56 documents were finally selected for generalization and analysis. RESULTS AND CONCLUSION: (1) The main pathogenesis of periodontitis is that periodontal pathogenic bacteria stimulate the organism, leading to changes in the periodontal microenvironment, breaking the original immune balance and releasing a variety of inflammatory factors, triggering an inflammatory response resulting in destruction of periodontal tissues. Necroptosis can modulate the immuno-inflammation in periodontal tissues, thus affecting the development of periodontitis. (2) The occurrence of necroptosis is related to a variety of proteins, signaling pathways, and signaling molecules. Animal experiments have confirmed that the expression of phosphorylated mixed lineage kinase domain-like protein (pMLKL) is related to the degree of inflammation, and RIP3 and pMLKL are highly expressed in the periodontal tissues of mice suffering from periodontitis. Blocking the RIP3/MLKL pathway is conducive to the reduction of inflammation in periodontal tissues and the control of periodontitis progression. (3) To explore whether pMLKL can be used as a diagnostic indicator of periodontitis is of great value in the prevention, diagnosis and treatment of periodontitis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Meta-analysis of the correlation between phase angle and sarcopenia and its diagnostic indexes Chen Jiayi, Li Huijing, Nong Yuxuan, Yin Yunfang, Liu Xiaobo, Chen Yue, Hu Xiaoshen, Zhong Dongling, Li Juan, Liu Tianyu, Jin Rongjiang 2025, 29 (12):  2575-2589.  doi: 10.12307/2025.358 Abstract ( 209 )   PDF (2353KB) ( 82 )   Save METHODS: The PubMed, EMbase, Cochrane Library, Web of Science, CNKI, WanFang Data, VIP and SinoMed databases were electronically searched to collect studies on the correlation between phase angle and sarcopenia and its diagnostic indexes from database inception to May 8, 2024. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 and Stata 14.0 software. RESULTS: A total of 50 eligible articles were included. Meta-analysis results showed that compared with the non-sarcopenic population, the phase angle was significantly reduced in sarcopenic patients [standardized mean difference (SMD)=-0.99, 95% confidence interval (CI) (-1.09, -0.90), P < 0.000 01]. The results of subgroup analysis indicated that the difference of phase angle was more significant in patients with severe sarcopenia and Asian sarcopenia. Moreover, reduction in the phase angle was more obvious in patients with malignant tumors and respiratory diseases with sarcopenia. And skeletal muscle mass index (Pearson’s r=0.565, P < 0.000 01), grip strength (Pearson’s r=0.446, P < 0.000 01), and gait speed (Pearson’s r=0.405, P < 0.000 01) all showed a moderate positive correlation with phase angle. However, appendicular skeletal muscle mass index showed a very weak positive correlation with phase angle (Pearson’s r=0.139, P=0.02). CONCLUSION: Phase angle has a significant difference between sarcopenia and non-sarcopenia population, and it is correlated with the diagnostic indexes of sarcopenia to different extents. It suggests that phase angle has some clinical values in the objective diagnosis of sarcopenia. However, the results may be influenced by some factors such as sarcopenia severity and detection instruments of phase angle. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effect of low-volume high-intensity interval training on cardiovascular risk factor in obese or overweight populations: a Meta-analysis  Li Xiupeng, Su Yuying, Wang Yuetong, Peng Liang, Wang Yida, Jing Wen 2025, 29 (12):  2590-2604.  doi: 10.12307/2025.372 Abstract ( 206 )   PDF (5099KB) ( 167 )   Save OBJECTIVE: This study comprehensively and quantitatively evaluates the effect of low-volume high-intensity interval training (LV-HIIT) on the prevention of cardiovascular disease in obese or overweight people through a meta-analysis, and further verifies the feasibility of LV-HIIT application in special populations such as obese people. METHODS: Literature addressing randomized controlled trials of LV-HIIT-related studies was searched in CNKI, PubMed, Web of Science, Cochrane library, and EBSCO-SPORTD Exercise Science full-text database from database inception to February 2024. Screening, quality assessment and data extraction of included studies were performed by two researchers, and Meta-analyses of outcome indicators, including combined effect sizes, subgroup analyses, Leave-One-Out sensitivity analyses, as well as the publication of Egger's test and the plotting of funnel plots, were performed using the software Review Manager 5.4 and the software Stata 17.0. The protocol was registered with the International Prospective Registry for Systematic Reviews (CRD42024534409). RESULTS: (1) Finally, 13 randomized controlled trials, including 349 subjects, were eligible and included, and the overall quality of the included literature was high. (2) LV-HIIT intervention significantly improved cardiorespiratory fitness [standardized mean difference (SMD)=-0.65, 95% confidence interval (CI): -0.87 to -0.43, P < 0.05], systolic blood pressure (SMD=0.38, 95% CI: 0.11-0.65, P < 0.05), diastolic blood pressure (SMD=0.42, 95% CI: 0.15-0.68, P < 0.05), and body fat percentage (SMD=0.25, 95% CI: 0.02-0.49, P < 0.05). (3) LV-HIIT and moderate-intensity continuous training (MICT) had similar interventional effects on cardiorespiratory fitness, systolic blood pressure, diastolic blood pressure, body fat percentage, standardized body weight, body mass index, high-density lipoprotein, low-density lipoprotein, and total cholesterol in people with overweight or obesity (P > 0.05), but MICT was better than LV-HIIT in improving triglyceride level (SMD=-0.30, 95% CI: -0.57 to -0.02, P < 0.05). (4) The results of subgroup analyses further showed that LV-HIIT and MICT interventions showed similar improvements in each index. CONCLUSION: Current evidence suggests that LV-HIIT can effectively enhance cardiopulmonary adaptive capacity and promote fat loss and blood pressure regulation in overweight or obese people, and the improvements are similar to those of MICT. Short-term LV-HIIT is more time-effective than long-term MICT. Future studies are recommended to determine the optimal LV-HIIT exercise prescription for overweight or obese populations.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Causal relationship between peripheral blood cells and osteoporosis Liu Kedi, Chen Yongxi, Qin Haibiao, Guo Shenghui, Qin Zhongshe, Meng Juewei, Cui Shanlin, Fan Junhong 2025, 29 (12):  2605-2613.  doi: 10.12307/2025.376 Abstract ( 207 )   PDF (2101KB) ( 72 )   Save BACKGROUND:  Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis, but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE: To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods.  METHODS: Genome-wide association study data sets on peripheral blood cells, overall bone density at different ages, and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data, with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting, MR-Egger, weighted median method, and simple median. The results were assessed for heterogeneity, pleiotropy, and sensitivity using Cochran’s Q, MR-Egger regression, and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION: Due to the heterogeneity revealed by Cochran’s Q test in the Mendelian randomization results, the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome, there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years [β=-0.07, 95% confidence interval (CI): -0.13, -0.01, P=0.02], a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05, 95% CI: 0.00, 0.10, P=0.037), a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04, 95% CI: -0.07, -0.01, P=0.005; β=-0.04, 95% CI: -0.07, -0.00, P=0.038), a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04, 95% CI: 0.01, 0.08, P=0.012; β=0.04, 95% CI: 0.00, 0.07, P=0.039), and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10, 95% CI: -0.16, -0.03, P=0.002). When heel bone mineral density was used as an outcome, there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04, 95% CI: -0.07, -0.01, P=0.016), and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05, 95% CI: 0.01, 0.08, P=0.007; β=0.05, 95% CI: 0.01, 0.08, P=0.004). To ensure the robustness of the results, meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count, there was a 5% reduction in the risk of decreased bone mineral density (OR=0.95, 95% CI: 0.94, 0.97, P < 0.001); whereas for every standard deviation increase in hemoglobin concentration and hematocrit, there was a 4% reduction in the risk of decreased bone density (OR=1.04, 95% CI: 1.03, 1.06, P < 0.001). In conclusion, increased white blood cell count in peripheral blood is a risk factor for bone mineral density; whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Relationship between hypertension and osteoporosis in different racial groups Zhang Yibo, Lu Jianqi, Mao Meiling, Chen Lidan, Lu Wei, Zhang Zheng, Zhang Yunli, Chen Jiayong 2025, 29 (12):  2614-2622.  doi: 10.12307/2025.380 Abstract ( 195 )   PDF (4714KB) ( 112 )   Save BACKGROUND: Observations from several clinical studies suggest a close relationship between hypertension and osteoporosis, but the causal relationship between hypertension and osteoporosis is unclear. OBJECTIVE: To determine whether there is a causal relationship between hypertension and osteoporosis, multisite bone mineral density and osteoporosis with fractures in Asian and European populations, respectively, using a comprehensive two-sample Mendelian randomized analysis. METHODS: Data of osteoporosis in Asian populations were obtained through Japan biological bank. Data of osteoporosis in European populations were obtained from UK Biobank, a British biological bank. Data of hypertension, multisite bone mineral density and osteoporosis with fractures were all from FinnGen R10 database. Inverse variance weighted method, MR-Egger regression method, weighted median method, weighted model method and simple model method were used to study the causal relationship between hypertension and osteoporosis, multisite bone mineral density and osteoporosis with fracture in Asian and European populations. Comprehensive sensitivity analysis was used to verify the robustness, heterogeneity and level pleiotropy of the results. Stsiger test was used to determine whether there was a reverse causal relationship between osteoporosis and hypertension. RESULTS AND CONCLUSION: In Asian populations, there was no significant genetic predictive causal relationship between hypertension and osteoporosis, and there was a positive causal relationship between hypertension and calcaneal bone mineral density. In European populations, hypertension had a negative causal relationship with osteoporosis, and there was no significant causal relationship between hypertension and systemic bone mineral density, calcaneal bone mineral density, forearm bone mineral density and osteoporosis with fracture. According to the stsiger test, there was no reverse causal relationship between osteoporosis, multiplesite bone mineral density, osteoporosis with fracture and hypertension in Asian and European populations. These results indicate that there is a causal relationship between hypertension and osteoporosis, that is, in Asian populations, hypertension and calcaneal bone mineral density show a positive causal relationship; in European populations, hypertension and osteoporosis show a negative causal relationship, but no reverse causal relationship. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Causal association between cathepsins and bone mineral density: two-way Mendelian randomization analyses Jiang Nan, Fu Haonan, Hao Yuhan, Chen Zhilin, Zhu Zhiqing, Xu Feng, Yu Dong 2025, 29 (12):  2623-2630.  doi: 10.12307/2025.391 Abstract ( 217 )   PDF (2887KB) ( 127 )   Save BACKGROUND: Previous studies have indicated that cathepsin K can intervene with the occurrence and development of osteoporosis by regulating bone mineral density in middle-aged and older adults. However, whether there is a causal relationship between the cathepsin family and bone mineral density in other populations remains unknown. OBJECTIVE: To investigate the causal relationship between cathepsin and bone mineral density. METHODS: Genetic loci associated with eight cathepins were extracted from the IEU Open GWAS database as instrumental variables, and bone mineral density values in five age groups acted as an outcome. The causal relationship between cathepin and bone mineral density was assessed by two-way Mendelian randomization analysis. Heterogeneity of the genetic instrumental variables was assessed using Cochran’s Q test, pleiotropy was assessed using the MR-Egger intercept test, and the sensitivity of single nucleotide polymorphisms used as instrumental variables to the causal effect of exposure and outcome was assessed using the leave-one-out method. RESULTS AND CONCLUSION: The results of the inverse variance weighting method with positive Mendelian randomization showed that cathepin H was negatively associated with bone mineral density in people aged 45-60 years [odds ratio (95% confidence interval)=0.965(0.94-0.99), P=0.04]; cathepin Z was negatively associated with bone mineral density in people aged 30-45 year [odds ratio (95% confidence interval)=1.06 (1.00-1.11), P=0.03]. The results of sensitivity analysis showed a stable causal relationship, and MR-Egger intercept analysis did not detect potential horizontal pleiotropy. The inverse Mendelian randomization results showed that bone mineral density had no significant inverse effect on cathepin. The above results confirm that cathepin can affect bone mineral density in some age groups, which may increase the risk of osteoporosis and should be given more attention. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Causal relationship between visceral adipose tissue and osteoarthritis Sun Pengcheng, Zhang Xiaoyun, Li Zhengpeng, Li Yongjin, Gao Zhengang, Li Kunjian 2025, 29 (12):  2631-2640.  doi: 10.12307/2025.374 Abstract ( 226 )   PDF (4729KB) ( 199 )   Save BACKGROUND: Although obesity is associated with osteoarthritis, it remains unclear whether visceral adipose tissue has a causal relationship with osteoarthritis.  OBJECTIVE: To investigate the causal relationship between visceral adipose tissue and osteoarthritis using two-sample Mendelian randomization methods.  METHODS: A total of 221 single nucleotide polymorphisms strongly associated with visceral adipose tissue without linkage disequilibrium were screened from the genome-wide association study (GWAS). Pooled data for osteoarthritis were derived from a large genome-wide association analysis that included up to 826 690 subjects (177 517 osteoarthritis patients and 649 173 controls) from nine different populations. We conducted two-sample Mendelian randomization analyses to assess the causal associations between visceral adipose tissue and early-onset any-site osteoarthritis (before age 45), any-site osteoarthritis, knee osteoarthritis, hip osteoarthritis, knee or hip osteoarthritis, spinal osteoarthritis, thumb osteoarthritis, and finger osteoarthritis. Inverse variance weighting was employed as the primary Mendelian randomization analysis method, with weighted median and MR-Egger methods used for supplementary clarification.  RESULTS AND CONCLUSION: Inverse variance weighting results revealed a positive causal effect of visceral adipose tissue on eight types of osteoarthritis: early-onset any-site osteoarthritis [odds ratio (OR)=1.91, 95% confidence interval (CI): 1.64-2.24, P=6.04×10-16], any-site osteoarthritis (OR=1.44, 95% CI: 1.38-1.49, P=3.65×10-75), knee osteoarthritis (OR=1.87, 95% CI: 1.75-2.00, P=1.29×10-79), hip osteoarthritis (OR=1.34, 95% CI: 1.24-1.45, P=2.84×10-14), knee or hip osteoarthritis (OR=1.71, 95% CI: 1.62-1.80, P=2.97×10-83), spinal osteoarthritis (OR=1.42, 95% CI: 1.31-1.54, P=8.89×10-17), thumb osteoarthritis (OR=1.26, 95% CI: 1.10-1.44, P=6.21×10-4), and finger osteoarthritis (OR=1.29, 95% CI: 1.13-1.49, P=2.68×10-4). Sensitivity analyses showed no heterogeneity, pleiotropy, or outliers in the causal effects of visceral adipose tissue on the eight types of osteoarthritis. These findings indicate that visceral adipose tissue is a risk factor of osteoarthritis, and excessive visceral adipose tissue may increase the risk of osteoarthritis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics