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28 June 2025, Volume 29 Issue 18 Previous Issue    Next Issue

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Passage-associated senescence decreases osteogenic activity of MC3T3-E1 cells via primary cilia  Gao Feng, Wang Jiliang, Wang Hongbo, Yang Yongsheng, Liu Yuan, Fu Su 2025, 29 (18):  3741-3746.  doi: 10.12307/2025.666 Abstract ( 198 )   PDF (1497KB) ( 58 )   Save BACKGROUND: In the repair of large bone defects, a variety of factors such as seed cell passaging can cause senescence of osteoblasts, leading to a reduction in osteogenic differentiation activity after implantation of tissue-engineered bone. In recent years, a novel mechanism involving primary cilia in cell senescence has been widely studied, but the primary cilia-related mechanism of "passage senescence - reduced osteogenic activity" is not fully understood. OBJECTIVE: To explore the possible mechanisms by which primary cilia regulate the senescence of MC3T3-E1 cells. METHODS: The osteoblast precursor cell lines MC3T3-E1 were passaged to 10th generation cells (early passage) and 40th generation cells (late passage). siRNA was used to silence IFT88 to inhibit primary cilia formation. The cells were than grouped into passage 10 group, passage 40 group, passage 10+siRNA IFT88 group, and passage 40+siRNA IFT88 group. RT-PCR and western blot assays were used to detect the expression of the aging marker P16 (CDKN2A), the osteogenic activity markers bone morphogenetic protein 2 and alkaline phosphatase, and the Hedgehog pathway IHH expression. Alizarin red staining and primary cilia immunofluorescence staining were performed. Spearman correlation analysis was conducted to analyze primary cilia positive rate and IHH and bone morphogenetic protein 2 expression.  RESULTS AND CONCLUSION: (1) The expression of CDKN2A (P16) in the passage 10 group was significantly higher than in the passage 40 group, but the difference disappeared after siRNA IFT88 intervention. (2) Meanwhile, the positive rate of primary cilia cells in the passage 10 group were higher than in the passage 40 group, while siRNA IFT88- significantly inhibited the expression of primary cilia in both passage 10 and passage 40 cells. (3) The transcriptional activity and protein expression of bone morphogenetic protein 2 and alkaline phosphatase in the passage 10 group were higher than those in the passage 40 group. After inhibiting the expression of primary cilia with siRNA, the above differences were reduced or disappeared. (4) The positive rate of primary cilia cells was correlated with IHH and bone morphogenetic protein 2 protein expression. To conclude, primary cilia mediate the replicative senescence of osteogenic MC3T3-E1 cells and regulate osteogenic differentiation ability.  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 identification of hub genes and their role in immune infiltration in osteoarthritis  Cai Wei, Zhu Yukun, Xu Jianzhong 2025, 29 (18):  3747-3757.  doi: 10.12307/2025.704 Abstract ( 188 )   PDF (4608KB) ( 189 )   Save BACKGROUND: Low-grade, chronic inflammation is thought to play a central role in the pathogenesis of osteoarthritis. However, the specific molecular mechanisms are still unclear.  OBJECTIVE: To screen and explore the potential hub genes and immune cell infiltration in osteoarthritis. METHODS: We merged data from the GSE206848 on the GPL570 and the GSE55235 and GSE55457 on the GPL96 to form the row dataset. Outlier samples were removed using weighted gene co-expression network analysis, followed by the identification of differentially expressed genes, and subsequent functional enrichment analysis of differentially expressed genes. Further, a protein-protein interaction network of differentially expressed genes was constructed, and hub genes were identified using two different algorithms in Cytoscape. Additionally, the CIBERSORT algorithm was employed to assess differences in immune cell infiltration proportions between osteoarthritis samples and normal controls. Finally, the diagnostic efficacy of hub genes for osteoarthritis was validated using quantitative reverse transcription polymerase chain reaction experiments conducted on synovial tissue samples collected from patients with osteoarthritis, in conjunction with the GSE12021 dataset from the GPL96 sequencing platform as an independent dataset.  RESULTS AND CONCLUSION: After eliminating 5 outlier samples, we identified a total of 340 differentially expressed genes, comprising 159 up-regulated genes and 181 down-regulated genes. Six hub genes were obtained by weighted gene co-expression network analysis and Cytoscape. CIBERSORT analysis revealed a difference in the proportion of multiple types of immune cell infiltration in osteoarthritic tissues compared with normal tissues. Moreover, the expression levels of the six hub genes exhibited strong correlation with the relative proportion of multiple immune cells in osteoarthritis. The results of RT-qPCR indicated that the relative expression levels of the six genes were down-regulated relative to normal tissues. However, there was no significant difference in the expression of NFKBIA and PTGS2 (P > 0.05). Simultaneously, receiver operator characteristic curves in both the original and external datasets demonstrated that the six hub genes exhibited strong diagnostic capabilities for osteoarthritis (area under the curve > 0.8). To conclude, four hub genes, CDKN1A, MYC, C-X-C motif chemokine ligand 2, and vascular endothelial growth factor A, are finally identified and may serve as molecular targets for future treatment by mediating immune response and inflammatory processes. 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 ultrasound-guided needle-knife on matrix homeostasis of rabbit cartilaginous endplate Hu Binhan, Chen Can, Huang Maochang, Zhao Yu, Liu Junning, Niu Susheng, Zhang Yan 2025, 29 (18):  3758-3766.  doi: 10.12307/2025.647 Abstract ( 122 )   PDF (3255KB) ( 168 )   Save BACKGROUND: Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration. Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration. Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified. OBJECTIVE: To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate. METHODS: A total of 24 male New Zealand rabbits were randomly divided into a control group (n=6) and a modeling group (n=18). Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks. After modeling, the modeling group was randomly divided into model group, needle-knife group and fake needle knife group, with 6 rabbits in each group. In the needle-knife group, the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina, while in the fake needle-knife group, the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina, with a total of four interventions, each time at an interval of 1 week. No intervention was performed in the control and model groups. Thirty days after the intervention, the disc degeneration was observed by MRI. The morphology of L7/S1 intervertebral disc cartilaginous endplate, nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored. The expressions of type II collagen, proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry. RESULTS AND CONCLUSION: MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group (P < 0.01), and higher in the needle-knife group than in the model group and the fake needle-knife group (P < 0.05). Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus, thinning of the cartilaginous endplate, and obvious calcification at the junction with bone endplate in the model group. The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group. The morphological scores of the model group, needle-knife group and fake needle-knife group were significantly higher than those of control group (P < 0.01). The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group (P < 0.01). Immunohistochemistry results showed that compared with the control group, the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased (P < 0.01), while the expression of matrix metalloproteinase-13 was significantly increased (P < 0.01). Compared with the model group and fake  needle-knife group, the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group (P < 0.05), while the expression of matrix metalloproteinase-13 was decreased significantly (P < 0.01). In conclusion, the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc. 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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RNA sequencing and quantitative proteomics analyses of molecular mechanism of medical ozone therapy for rabbit skeletal muscle injury Ruan Zhen, Kou Jiushe 2025, 29 (18):  3767-3774.  doi: 10.12307/2025.636 Abstract ( 168 )   PDF (2925KB) ( 145 )   Save BACKGROUND: As a new treatment method, local injection of medical ozone has anti-inflammatory, analgesic and immunomodulatory effects on injured skeletal muscle tissue, but its mechanism of action is still lacking systematic research. OBJECTIVE: To observe the intervention effect of medical ozone on skeletal muscle crush injury of rabbit models, and to analyze the differential gene expression of injured rabbit tibialis anterior muscle after ozone treatment through RNA-sequencing and tandem mass tag labeled quantitative proteomic technology, in order to partially reveal the molecular mechanism of medical ozone treatment for skeletal muscle injury.  METHODS: Eighteen Japanese white rabbits were randomly divided into a blank group, a model group, and an ozone group, with 6 rabbits in each group. Rabbit tibialis anterior muscle compression injury models were established in the latter two groups. After 12 hours of model establishment, 2 mL of medical ozone with a mass concentration of 30 μg/mL was injected into the injured muscle of rabbits in the ozone group. Tissue samples were taken 3 days after ozone treatment. Hematoxylin-eosin staining was used to observe the morphological changes of skeletal muscle. RNA sequencing and tandem mass spectrometry tag were used to detect rabbit tibialis anterior muscle tissue. Bioinformatics analysis was used to explore the biological processes of differentially expressed genes and proteins between groups and then to investigate the molecular mechanism of ozone treatment of skeletal muscle injury.   RESULTS AND CONCLUSION: After 3 days of ozone treatment, compared with the blank group, the model group showed swelling of cells, infiltration of inflammatory cells, and partial dissolution of muscle fibers. Compared with the model group, cell edema was alleviated and the number of inflammatory cells was reduced in the ozone group. (2) The results of RNA sequencing and bioinformatics analysis showed that compared with the blank group, 596 differentially expressed genes were screened in the model group. Compared with the model group, 405 differentially expressed genes were screened in the ozone group. There were a total of 194 differentially expressed genes shared among these differentially expressed genes. Proteomic analysis results exhibited that compared with the blank group, the model group contained 138 differentially expressed proteins. Compared with the model group, 242 differentially expressed proteins were determined in the ozone group. There were 66 differentially expressed proteins shared between the two comparison groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on differentially expressed genes/proteins, and it was found that they were mainly enriched in the PI3K-Akt signaling pathway, Ras signaling pathway, and MAPK signaling pathway. It is indicated that medical ozone may promote the repair of injured muscle through regulating PI3K/Akt/NF-κB and Ras/MAPK/NF-κB signaling pathway by acting on target genes, such as Syk, FGF16, CSF-1, and MRAS. 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 acupotomy on the expression of fibroblast growth factor family and its receptor in the splenius capitis muscles of rats with cervical spondylosis  Liu Fushui, Qian Jiaming, Fang Ting, Khaliunaa Tumurbaatar, Zhao Xiaolan, Zhu Jinchao, Wang Xiaole 2025, 29 (18):  3775-3783.  doi: 10.12307/2025.642 Abstract ( 151 )   PDF (3280KB) ( 73 )   Save BACKGROUND: Acupotomy is an effective method for the treatment of cervical spondylosis with definite clinical efficacy, but its key molecular mechanism is still unclear. OBJECTIVE: To observe the effect of acupotomy intervention on the expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles of rats with cervical spondylosis, and to study the therapeutic mechanism of acupotomy in cervical spondylosis. METHODS: The Genomics Expression Omnibus Database was searched to obtain the microarray dataset GSE153761, which was compatible with the study, and a bioinformatics approach was used for the initial screening of targets, followed by animal experiments. Twenty-four 6-month-old SPF grade Sprague-Dawley rats were randomly divided into four groups. The model of cervical spondylosis was established by unbalanced dynamic and static forces in the model and acupotomy groups. The muscles and ligaments were not cut in the sham operation group. After successful modeling, acupotomy intervention was performed in the acupotomy group, once a week, 3 times in total. Normal rats were selected as controls. The posteroanterior and lateral X-rays of the cervical spine were taken for modeling verification; the open-field tests were performed in all rats to observe behavioral changes; the pathological structure of the splenius capitis muscles was observed by hematoxylin-eosin staining; the mRNA and protein expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles was detected by fluorescent quantitative PCR and immunohistochemical method, respectively. RESULTS AND CONCLUSION: Bioinformatics results indicated that fibroblast growth factor family/kinase insert domain protein receptor is an important signal axis for activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. After modeling, the intervertebral space of the rats was narrowed, and the anterior and posterior borders of the vertebral body and the articular process were hyperosteogenous. In the open-field tests, the total distance and average speed in the model group were decreased after modeling (P < 0.05), while the total rest time in the model group was increased (P < 0.05). After treatment, the total distance and average speed in the acupotomy group were greater than those in the model group (P < 0.05), while the total rest time in the acupotomy group was shorter than that in the model group (P < 0.05). The pathological changes of the splenius capitis muscles indicated damage to the cervical muscle, and acupotomy improved cervical muscle strain. Compared with the normal group, The mRNA and protein expressions of fibroblast growth factor 7, fibroblast growth factor 9, fibroblast growth factor 10, fibroblast growth factor 18, and kinase insert domain protein receptor in the splenius capitis muscles were increased in the model group compared with the normal group (P < 0.05). In contrast, acupotomy treatment could downregulate the above indicators (P < 0.05). Thus, acupotomy may repair cervical muscle strain by regulating the expression of fibroblast growth factor 7, fibroblast growth factor 9, fibroblast growth factor 10, fibroblast growth factor 18, and kinase insert domain protein receptor, thereby improving intervertebral disc degeneration, which may be the key target for acupotomy treatment of cervical spondylosis. 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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Immediate effects of different stretching methods on knee joint muscle strength and vertical jump performance of healthy adults Zhao Yuhan, Li Yamei, Yan Shifang, Jiang Huabei 2025, 29 (18):  3784-3790.  doi: 10.12307/2025.681 Abstract ( 194 )   PDF (1371KB) ( 95 )   Save BACKGROUND: Static stretching effectively improves joint motion amplitude, dynamic stretching effectively improves muscle strength and athletic performance through the post-activation strengthening effect of the muscles. OBJECTIVE: To explore the immediate effects of different stretching methods on knee joint muscle strength and vertical jump performance, and provide theoretical support for seeking the best stretching plan, improving sports performance, and preventing training injuries.  METHODS: Thirty healthy college students were randomly recruited. The Biodex isokinetic muscle strength system, Qualisys infrared motion capture system, and AMTI three-dimensional force measurement platform were used to collect knee joint muscle strength and vertical jump data after static quadriceps/hamstring stretching, dynamic quadriceps/hamstring stretching, dynamic quadriceps/ static hamstring stretching, and static quadriceps/dynamic hamstring stretching. The peak torque, average power, vertical jump height, peak vertical ground reaction force, and joint motion amplitude of the knee joint were used to evaluate the muscle strength and vertical jump performance of the knee joint.  RESULTS AND CONCLUSION: Compared with the static quadriceps/hamstring stretching, dynamic quadriceps/hamstring stretching significantly increased knee joint peak torque, average power, and vertical jump height (P < 0.05); dynamic quadriceps/static hamstring stretching and static quadriceps/dynamic hamstring stretching significantly increased knee extension and flexion peak torque and average power (P < 0.05). Compared with static quadriceps/hamstring stretching, second peak vertical ground reaction force significantly decreased after static quadriceps/dynamic hamstring stretching (P < 0.05); lower limb joint motion amplitude significantly increased after dynamic quadriceps/hamstring stretching (P < 0.05). These findings indicate that immediate agonists/antagonistic muscle dynamic stretching and agonists dynamic stretching/antagonistic muscle static stretching significantly improve knee joint muscle strength, vertical jump performance, and joint motion amplitude. A larger joint motion amplitude is beneficial for improving athletic performance and better absorbing ground impact during landing. At the same time, agonists muscle dynamic stretching/antagonistic muscle static stretching is better than agonists/antagonistic muscle dynamic stretching to improve knee joint muscle strength, and agonists muscle static stretching/antagonistic muscle dynamic stretching is beneficial for improving the energy absorption capacity during vertical jumping and reducing the risk of injury during landing.  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 different forms of shaker exercises on hyoid muscles activation in healthy adults  Li Zhenzhen, Zhen Qiaoxia, Chen Keke, Fang Boyan 2025, 29 (18):  3791-3797.  doi: 10.12307/2025.652 Abstract ( 179 )   PDF (1370KB) ( 88 )   Save BACKGROUND: Shaker exercise can enhance the contraction force of the hyoid muscles, which is effective in the treatment of oropharyngeal dysphagia. Shaker exercise should be performed through the main force of the anterior cervical region to train the hyoid muscles. However, patients often experience physical fatigue, leading to compensatory abdominal force exertion. Moreover, the effect of different forms of shaker exercises on the activation of the hyoid muscles in healthy adults is currently unknown. OBJECTIVE: To investigate the effects of shaker exercises with varying force on the activation of the hyoid muscles in healthy adults. METHODS: Twenty healthy adults, including 10 males and 10 females with a mean age of (26.8±3.4) years were recruited as participants for the study. They performed isometric movements of the shaker exercise in the anterior neck and abdominal force modes in sequence. Simultaneously, real-time surface electromyography data were collected from the suprahyoid and infrahyoid muscles and rectus abdominis muscle. At the end of the experiment, participants were asked to rate the physical exertion levels for each type of force using the Borg Rating of Perceived Exertion Scale at the end of the training. Following a series of processing of the original electromyography signals, the peak amplitude and/or average amplitude values of the suprahyoid and infrahyoid muscles and rectus abdominis in the 60-second movement window were calculated and compared, and the differences in the subjective fatigue scores corresponding to the two force modes were compared. RESULTS AND CONCLUSION: The average amplitude of the rectus abdominis muscle in the abdominal force mode was found to be higher than that in the neck force mode (P < 0.05). However, there were no significant differences in the mean and peak amplitudes between the suprahyoid and infrahyoid muscles in the two force modes (P > 0.05). There was also no significant difference in the Borg Rating of Perceived Exertion Scale scores in the two force modes (P > 0.05). These findings suggest that shaker exercises with different force modes (anterior neck and abdomen) have minimal impact on the hyoid muscles and similar feeling of fatigue in healthy adults. 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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Gluteal muscle activation exercise therapy improves lower limb muscle strength in young male patients with anterior knee pain Wu Yue, Ren Shuang, Huang Hongshi, Dai Ruilan, Ao Yingfang, Gou Bo 2025, 29 (18):  3798-3803.  doi: 10.12307/2025.656 Abstract ( 283 )   PDF (1092KB) ( 120 )   Save BACKGROUND: It has been found that anterior knee pain is related to the biomechanics of the lower limbs, but there is still a lack of research on the effects of gluteal muscle training on the knee joint and daily activities of the lower limbs.  OBJECTIVE: To investigate the effects of gluteal muscle activation exercise therapy on the muscle strength of hip and knee joint muscle groups and pain in young male patients with anterior knee pain.  METHODS: Twenty-five young male patients with anterior knee pain were enrolled and randomly divided into two groups: gluteal muscle activation group (n=12) and blank control group (n=13). The gluteal muscle activation group performed gluteal muscle activation exercises, 40 minutes each, 3 times/week, for 6 weeks. The blank control group did not perform any intervention. Assessments were conducted at the time of enrollment and again after 6 weeks. The relative peak torque, total work, ratio of flexors and extensors, and muscle endurance values of the affected hip and knee joints were evaluated through isokinetic flexion and extension tests at 60 (°)/s and 180 (°)/s. At the same time, floors at which climbing was stopped in the stair-climbing test were detected and the visual analog scale score was assessed.  RESULTS AND CONCLUSION: (1) Isokinetic knee extension and flexion test: For the hip joint, the gluteal muscle activation group showed a significant increase in the relative peak torque at 60 (°)/s and 180 (°)/s by 29.74% and 25.95% respectively after intervention (P=0.022, P=0.024); the blank control group showed a 12.12% decrease in muscle endurance at 180 (°)/s compared to before intervention (P=0.000). For the knee joints, the gluteal muscle activation group had a significant increase in the relative peak torque at 60 (°)/s and 180 (°)/s by 18.69% and 7.27% respectively after intervention (P=0.006, P=0.033); there were no significant changes in the blank control group before and after intervention (P > 0.05). (2) Stair-climbing test: The number of floors climbed to cessation in the gluteal muscle activation group was (6.41±6.1) floors, which was higher than that in the blank control group (P=0.024), and increased by 33.11% compared with before intervention (P=0.016); there were no significant changes in all the indicators of the blank control group before and after intervention (P > 0.05). (3) Pain assessment: After intervention, the visual analogue scale score of the gluteal muscle activation group was significantly lower than that of the blank control (P=0.036), and also decreased compared to before intervention (P=0.000); there were no significant changes in the blank control group before and after intervention (P > 0.05). To conclude, the 6-week gluteal activation exercise therapy can improve the explosive power and endurance of the lower limb muscles, and reduce the degree of anterior knee pain. For patients with anterior knee pain, gluteal muscle training is necessary to promote recovery. 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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Autologous scalp repair of wounds in the medium-thickness skin donor area: safety and effectiveness Cao Dayong, Zheng Junjie, Wang Lei, Yang Yang, Guo Haina, Xing Peipeng, Xia Chengde, Di Haiping 2025, 29 (18):  3804-3810.  doi: 10.12307/2025.664 Abstract ( 149 )   PDF (1640KB) ( 101 )   Save BACKGROUND: Large deep burn wounds are often accompanied by scar hyperplasia after healing, requiring transplantation of medium-thickness skin for repair, and the medium-thickness skin slices taken generally reach below the papillary layer of the dermis. If not handled correctly, complications such as delayed healing, ulceration, and post-healing pain and itching in the donor area can easily occur. Therefore, the repair of wounds in the donor area should be emphasized. OBJECTIVE: To observe the safety and practicability of autologous scalp repair of skin donor area in patients with deep burns and scarring.  METHODS: Sixty patients with deep burn and scar hyperplasia admitted to the Burn Department of Zhengzhou First People’s Hospital from January 2021 to September 2023 were selected as the study subjects. They all needed medium-thickness skin transplantation and repair, and were divided into study group (n=30) and control group (n=30) according to random systematic sampling method. The skin was taken from the patient's own medium-thickness skin on the leg or back. In the study group, the skin donor area was repaired with self-blade thick scalp replantation, and in the control group, the skin donor area was repaired with absorbent dressing. The wound healing rate and the time to complete epithelialization of the wound were observed and compared in the two groups 6 days after surgery. The pain of dressing change at 3 and 6 days after surgery and scar hyperplasia in the skin donor area at 6 months after surgery were compared between two groups.  RESULTS AND CONCLUSION: Compared with the control group, the time to complete epithelialization of the wound was significantly lower in the study group (P < 0.05), and the wound healing rate was significantly higher in the study group (P < 0.05), the pain score for dressing change at 3 and 6 days after surgery was significantly lower in the study group (P < 0.05), and the scar hyperplasia rate, scar score and itch score were also significantly lower in the study group (P < 0.05) at 6 months after surgery. In conclusion, autologous scalp repair of the medium-thickness skin donor area can accelerate wound healing and reduce scar hyperplasia. 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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Neuroprotective mechanism of electroacupuncture in cerebral ischemia-reperfusion model rats Wu Haiyang, Duan Mian, Li Chenglong, Zhang Junyu, Ji Haisheng, Wang Haitao, Mao Wei, Wang Ying 2025, 29 (18):  3811-3818.  doi: 10.12307/2025.653 Abstract ( 159 )   PDF (1943KB) ( 93 )   Save BACKGROUND: Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis, but the upstream regulatory mechanisms are not yet fully clarified. OBJECTIVE: To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury. METHODS: Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery, model, and electroacupuncture groups, with nine rats in each group. Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups. The electroacupuncture group was subjected to electroacupuncture at “Baihui,” “Fengfu,” and “Dazhui” acupoints, 20 minutes each, once a day, for 7 consecutive days. After treatment, neurological deficit scoring and pole test were performed to assess behavioral changes. Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats. Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats. Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats, ELISA method was used for measuring interleukin-1β, interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats. Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein, nod-like receptor associated protein 3 (NLRP3), Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively, and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.  RESULTS AND CONCLUSION: (1) Compared with the sham surgery group, rats in the model group showed an increase in neurological deficit score, pole test score, cerebral infarction volume (P < 0.05), the immunofluorescence expression of Iba-1 and reactive oxygen species (P < 0.05), the levels of interleukin-1β, interleukin-6 and tumor necrosis factor α (P < 0.05), and the mRNA and protein expression of thioredoxin interaction protein, NLRP3, Caspase-1 and interleukin-1β in cerebral cortex tissue (P < 0.05). Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis, with fragmented and dissolved nuclei and cellular vacuoles. (2) Compared with the model group, rats in the electroacupuncture group showed a reduction in neurological deficit score, pole climbing test score, cerebral infarction volume (P < 0.05), the immunofluorescence expression of Iba-1 and reactive oxygen species (P < 0.05), the levels of interleukin-1β, interleukin-6 and tumor necrosis factor α (P < 0.05), and the mRNA and protein expression of thioredoxin interaction protein, NLRP3, Caspase-1 and interleukin-1β in cerebral cortex tissue (P < 0.05). Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated, with significantly reduced cell necrosis and vacuolation. (3) Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group. To conclude, electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury, possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors. 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 Buyang Huanwu Tang and its main components on pyroptosis in brain tissue of rats with middle cerebral artery occlusion and reperfusion Wang Ruikun, Gao Weijuan, Zhang Haoran, Liu Yijie, Bu Jiaxin, Yuan Mei, Qin Yuxin, Zhang Yi 2025, 29 (18):  3819-3825.  doi: 10.12307/2025.670 Abstract ( 168 )   PDF (3598KB) ( 79 )   Save BACKGROUND: Cellular pyroptosis is an important pathological mechanism of cerebral ischemia/reperfusion injury. Buyang Huanwu Tang is a classic formula for the clinical treatment of ischemic stroke in traditional Chinese medicine, and cellular pyroptosis may be an effective target of Buyang Huanwu Tang in the treatment of cerebral ischemia/reperfusion injury. OBJECTIVE: To observe the effect and mechanism of Buyang Huanwu Tang on pyroptosis in brain tissues of middle cerebral artery occlusion/reperfusion rats. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into sham operation group, model group, Astragalus membranaceus group and Buyang Huanwu Tang group. Except for the sham operation group, all groups were subjected to middle cerebral artery occlusion for ischemia for 2 hours and reperfusion for 72 hours. The rats in the Astragalus membranaceus group and Buyang Huanwu Tang group were continuously gavaged with the corresponding volume of drugs until ischemia and reperfusion for 72 hours after awakening from the modeling, once in the morning and once in the evening. Zea Longa score was used to observe the neurological deficits of rats. TTC staining was performed to observe cerebral infarct size in rats. Hematoxylin-eosin staining was used to observe the pathological changes of the brain tissue. Immunofluorescence was used to observe the co-expression of Tunel and Cleaved-Caspase-1 in the brain tissue and the expression of the junction protein ASC. Immunohistochemistry and western blot were used to detect the expression of pyroptosis-related proteins in rat brain tissues. RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the neurological deficit score of rats was significantly higher in the model group  (P < 0.01), and compared with the model group, the neurological deficit score of rats was significantly lower in the Buyang Huanwu Tang group and the Astragalus membranaceus group (P < 0.01). (2) Compared with the model group, the volume ratio of cerebral infarction was lower in the Astragalus membranaceus group and Buyang Huanwu Tang group (P < 0.01). (3) In the model group, the nuclei of neuronal cells in the brain tissue were deeply stained or lysed, and arrangement of the cells was disorganized. Compared with the model group, the pathologic damage of the brain was less severe in the Buyang Huanwu Tang group and the Astragalus membranaceus group. (4) Compared with the sham operation group, the number of Tunel and Cleaved-Caspase-1 double-positive cells and immunofluorescence intensity of ASC in the brain tissue was significantly increased in the model group, and the expression of Cleaved-Caspase-1, NLRP3, interleukin 18, and interleukin 1β was significantly elevated in the model group (P < 0.01). Compared with the model group, the number of Cleaved-Caspase-1 and Tunel double-positive cells, immunofluorescence intensity of ASC, and the expression of Cleaved-Caspase-1, NLRP3, interleukin 18, and interleukin 1β were all significantly decreased in the Buyang Huanwu Tang group and the Astragalus membranaceus group (P < 0.01). The results indicate that Buyang Huanwu Tang and its monarch drug Astragalus membranaceus can effectively alleviate brain tissue injury in rats with middle cerebral artery occlusion and reperfusion, and its mechanism may be related to the inhibition of neuronal cell pyroptosis. 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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A three-dimensional virtual simulation platform for Mongolian medical brain vibration therapy constructed based on the three-dimensional motion capture technology Bai Xue, Wang Xing, Hong Guoping, Jia Rushuo, Han Qi, Guo Huaiyu, Niu Hongkai, Zhang Shaojie, Chao Lumen 2025, 29 (18):  3826-3832.  doi: 10.12307/2025.641 Abstract ( 214 )   PDF (2419KB) ( 119 )   Save BACKGROUND: Three-dimensional (3D) Motion Capture Technology can build accurate, objective, and quantized medical virtual simulation model, which is conducive to clinical learners’ precise and in-depth understanding and mastery of various traditional therapies. The virtual simulation model of traditional Chinese medicine based on the 3D Motion Capture Technology has been reported, but such a system of traditional Mongolian medicine therapy has not been reported. OBJECTIVE: To construct an interactive 3D visualization virtual simulation model based on the 3D Motion Capture Technology. METHODS: Motion capture data of the professor of Mongolian Medicine Department were collected using the 3D optical motion capture system (Motion Analysis) and Plantar Force Platform. The 3D motion model of brain vibration therapy was constructed using Motion Builder software, and the role model was constructed using Maya software matched with the action model. Unity3D software was used to build a virtual simulation system of Mongolian medical brain vibration therapy. The system integrated information on 3D animation, kinematic and dynamic parameters of Mongolian medical brain vibration therapy. RESULTS AND CONCLUSION: By using 3D Motion Capture Technology and Computer Simulation Technology to reconstruct the operation of Mongolian medical brain vibration therapy, it can display the posture of the operator and subject and record the key parameters of spatial position and changes of joint motion to obtain kinematic and dynamic parameters. The interactive 3D virtual simulation technology is used to realize the visual presentation of 3D virtual simulation of Mongolian medical brain vibration therapy. It lays a foundation for the standardization, digitization and visualization of Mongolian medical brain vibration therapy. 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 by which eupatilin improves learning and memory abilities in rats with subarachnoid hemorrhage  Mo Menghui, Zhang Guangmou, Zhou Haiyan, Shi Lifen, Chang Lulu, Cheng Shuxin 2025, 29 (18):  3833-3839.  doi: 10.12307/2025.659 Abstract ( 147 )   PDF (2414KB) ( 58 )   Save BACKGROUND: Eupatilin, a flavonoid active component derived from Artemisia sinensis, has been reported to relieve inflammation and improve neurological scores in rats with subarachnoid hemorrhage, but its role and mechanism in learning and memory remain unclear.  OBJECTIVE: To investigate the effects of eupatilin on learning and memory abilities and P38 mitogen activated protein kinase (p38 MAPK)/signal transducer and activator of transcription-3 (STAT3) pathway proteins in rats with subarachnoid hemorrhage.  METHODS: A total of 50 Sprague-Dawley rats were randomly divided into sham surgery group, model group, eupatilin group, hesperetin group, eupatilin+hesperetin group, with 10 rats in each group. Except for the sham surgery group, the rats in the other groups were used to construct a subarachnoid hemorrhage model through intravascular perforation. Two hours after successful modeling, the eupatilin group was injected with 10 mg/kg eupatilin via the tail vein, the hesperetin group was injected with 50 mg/kg hesperetin (p38 MAPK/STAT3 signaling pathway activator) via the tail vein, the eupatilin+hesperetin group was injected with 10 mg/kg eupatilin and 50 mg/kg hesperetin via the tail vein, and the sham surgery group and the model group were injected with 10 mL/kg saline via the tail vein. The drug treatment lasted for 24 hours. The neurologic deficit score and Morris water maze experiment were applied to detect the neurological function and learning and memory abilities of rats. Hematoxylin-eosin staining was performed to detect the histopathological changes of the hippocampus. TUNEL method was used to detect neuronal apoptosis. Immunohistochemical staining was conducted to detect the number of doublecortin-positive cells in hippocampal tissue. Western blot was applied to detect the expression of p38 MAPK/STAT3 protein in hippocampal tissue.  RESULTS AND CONCLUSION: Compared with the sham surgery group, rats in the model group had lower neurological deficit scores, learning and memory abilities, and number of doublecortin-positive cells (P < 0.05), and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3 (P < 0.05). Compared with the model group, rats in the eupatilin group showed higher neurological deficit scores, learning and memory abilities, and number of doublecortin-positive cells (P < 0.05), and lower neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3 (P < 0.05), while those in the nerolone group showed lower neurological deficit scores, learning and memory abilities, and number of doublecortin-positive cells (P < 0.05), and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3 (P < 0.05). Compared with the eupatilin group, rats in the eupatilin+hesperetin group had lower neurological deficit scores, learning memory abilities, and number of doublecortin-positive cells (P < 0.05), and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3 (P < 0.05). Hematoxylin-eosin staining showed that compared with the model group, the nerve cells were more neatly arranged in the eupatilin group, disorganized in the hesperetin group, and arranged in a similar way to the model group in the eupatilin+hesperetin group. To conclude, eupatilin may improve learning and memory abilities of rats with subarachnoid hemorrhage by inhibiting the p38 MAPK/STAT3 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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Effect of the number of times to urinate on the modeling rate of neurogenic bladder model in rats after complete spinal cord transection Liang Roujun, Zhan Lifen, Zeng Xuejiu, Ding Qiangsheng, Luo Xiaojing, Zhuo Yue, Ai Kun, Deng Shifeng, Xu Ming, Zhang Hong 2025, 29 (18):  3840-3847.  doi: 10.12307/2025.680 Abstract ( 139 )   PDF (2331KB) ( 65 )   Save BACKGROUND: Spinal cord injury often leads to neurogenic bladder with hyperreflexia of the forced urethral muscle, but there is a lack of clear understanding of its pathogenesis and treatment, and establishing a stable and reliable animal model has an important impact on revealing its pathomechanisms and exploring therapeutic approaches. OBJECTIVE: To investigate the effect of the number of times to urinate on neurogenic model rats after complete spinal cord transection in order to improve the postoperative survival and modeling rate of neurogenic model rats. METHODS: Out of 46 female Sprague-Dawley rats, 6 were selected as the sham-operated group using the random number table method, and the remaining 40 rats were randomly divided into 0, 1, 3, and 5 times daily urination groups after complete spinal cord transection modeling, with 10 rats in each group. The residual urine volume was measured every 3 days within 19 postoperative days, and the survival and modeling were observed on the 19th day after the operation, and urodynamics tests and contraction experiments of isolated forced urethra muscle strips were performed. RESULTS AND CONCLUSION: (1) Survival and modeling rate: there was 10% survival rate and 10% modeling rate in the group of 0 times daily urination; 20% survival rate and 10% modeling rate in the group of 1 time daily urination; 70% survival rate and 70% modeling rate in the groups of 3 and 5 times daily urination. (2) Residual urine volume: compared with the sham-operated group, the residual urine volume of the groups of 3 and 5 times daily urination was significant increased on postoperative days 3, 6, 9, 12, and 15 (P < 0.01); the residual urine volume of the groups of 3 and 5 times daily urination was increased on the 18th day after surgery (P < 0.05). Compared with the 3 times daily urination group, the residual urine volume was decreased in the 5 times daily urination group on the 6th day after surgery (P < 0.05), while there was no significant difference in the residual urine volume between the 3 and 5 times daily urination groups on the 3rd, 9th, 12th, 15th, and 18th days after surgery. (3) Urodynamics: Compared with the sham-operated group, the differential pressure at the point of leakage was significantly reduced (P < 0.01) and the maximal volume was significantly increased (P < 0.01) in the 3 and 5 times daily urination groups. There was no statistical difference in the differential pressure at the point of leakage and the maximal volume between the 3 and 5 times daily urination groups. (4) Muscle-strip contraction test of isolated detrusor muscles: Compared with the sham-operated group, the contraction amplitude and frequency of detrusor muscle strips were significantly reduced in the 3 and 5 times daily urination groups (P < 0.01). There was no statistically significant difference in the contraction amplitude and frequency of detrusor muscle strips between the 3 and 5 times daily-urination groups. In conclusion, assisted urination is one of the keys to establish a successful neurogenic model of urethral reflexes, and there is no significant difference in the effects of urinating 3 or 5 times a day on the neurogenic model. It is recommended to urinate at least 3 times a day based on the actual workload and the modeling rate.  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 treadmill exercise on hippocampal autophagy-induced apoptosis in ovariectomized stressed rats  Song Yanli, Zhang Xi, Guo Yangbo, Ling Xiaomei, Li Linhai, Yang Zixin, Su Xiaoyun, Cui Jianmei 2025, 29 (18):  3848-3855.  doi: 10.12307/2025.640 Abstract ( 181 )   PDF (1431KB) ( 121 )   Save BACKGROUND: Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline. Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear. OBJECTIVE: To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.  METHODS: Forty Sprague-Dawely rats were randomly divided into four groups, namely, sham operation group (n=10), ovariectomized group (n=10), ovariectomized stress group (n=10) and ovariectomized stress exercise group (n=10). Except for the sham operation group, the ovaries were removed in the other three groups to establish a perimenopausal rat model, and then a depressed rat model was established by chronic unpredictable stress in the latter two groups. The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise. Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress. The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress. Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin (AMPK/mTOR/ULK1), hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.  RESULTS AND CONCLUSION: (1) Compared with the sham operation group, rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test. (2) Ovary removal reduced the learning memory capacity of rats, as evidenced behaviorally by a significant increase in the number of working memory errors, the number of reference memory errors, and the completion time, and an even more pronounced increase in the above measures in the ovariectomized stress group. (3) Compared with the ovariectomized group, there was a significant reduction in the number of working memory errors, the number of reference memory errors, and the completion time in the ovariectomized stress group. (4) Compared with the sham operation group, in the ovariectomized and ovariectomized stress groups, the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated, the expression of autophagy-related factors proteins Beclin-1 and LC3II, as well as the protein expression of AMPK and ULK1, was decreased, whereas the expression of mTOR protein was elevated. Changes in the above indicators were more significant in the ovariectomized stress group. (5) Compared with the ovariectomized stress group, in the ovariectomized stress exercise group, the protein expression of Caspase 3 was significantly decreased, the protein expression of Beclin-1 and LC3II was significantly increased, the protein expression of AMPK and ULK1 was significantly increased, and the protein expression of mTOR was significantly reduced. To conclude, 4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway, thereby enhancing the learning and memory capacity of rats with ovariectomized depression. 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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Molecular mechanism of active ingredients of Ligustri Lucidi Fructus against osteoporosis  Wang Wenchi, Xia Tian, Wu Ruiqi, Liang Haohan, Ni Zhenyang, Zhang Zhenhao, Li Zhenxing, Chen Guanghui, Su Han 2025, 29 (18):  3856-3867.  doi: 10.12307/2025.667 Abstract ( 146 )   PDF (2091KB) ( 120 )   Save BACKGROUND:  Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis, and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars. OBJECTIVE: To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo. METHODS: We searched the relevant literature included in CNKI and PubMed databases using the search terms of “Osteoporosis, Bone marrow mesenchymal stem cells, Osteoblast, Osteoclast, Ligustri Lucidi Fructus, Signal path” in Chinese and English, respectively. According to the needs of the research, we established the corresponding criteria and screened the literature. A total of 82 papers were included in the final review. RESULTS AND CONCLUSION: (1) The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following: Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1. This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts, while decreasing the expression of glycogen synthase kinase 3β. Further, it promotes the expression of β-catenin, runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus, thereby promoting the bone formation capacity of osteoblasts. The advantage is that it acts directly on osteoblasts to promote bone formation, which provides a new strategy for the treatment of osteoporosis. (2) Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats. In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin, while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand. This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system, demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism, but there is no significant effect on Ca2+ concentration, which may limit its use in some specific types of osteoporosis. (3) By decreasing the expression of phosphatidylinositol 3 kinase, reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos, pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts. This inhibition reduces the proliferation and maturation of osteoclasts, which can help to reduce bone resorption. The advantage of this inhibition is that it can directly target osteoclasts, which provides a new target for osteoporosis treatment. However, the specific regulatory mechanism of osteoclasts needs to be studied in depth, and its long-term effect and safety need to be further evaluated. (4) The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis, but their mechanism of action is complex, involving the interaction of multiple genes, proteins and signaling pathways. In the future, large-scale clinical trials need to be carried out to verify its effectiveness and safety, and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.  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 by which melatonin promotes bone regeneration and its application in oral implantation Ji Mingyi, Ji Xinyi, Xu Junfeng 2025, 29 (18):  3868-3876.  doi: 10.12307/2025.669 Abstract ( 196 )   PDF (1893KB) ( 178 )   Save BACKGROUND: Alveolar bone defects can jeopardize patients’ oral and jaw function and physical and mental health, and reduce their quality of life. Melatonin can be used for the prevention and treatment of bone defect diseases due to its properties of promoting bone regeneration, and also has important applications in osseointegration and peri-implant inflammation related to oral implants. OBJECTIVE: To explore the mechanism by which melatonin promotes bone regeneration, the potential application of melatonin in the field of oral implantation, and to provide new ideas for the utilization of melatonin’s osteogenic properties in oral implantation. METHODS: With “melatonin, bone defect, osteoblast, osteoclast, reactive oxygen species, periodontitis, osseointegration, peri-implantitis” as Chinese and English search terms, the relevant literature was searched in CNKI and PubMed databases. The timeframe of the search was from January 2019 to August 2024, while a few classical early documents were included. Screening was carried out by reading the titles and abstracts, and 91 papers were finally included for review. RESULTS AND CONCLUSION: (1) Melatonin promotes bone regeneration by promoting the proliferation and differentiation of osteoblasts, chondrocytes and vascular endothelial cells, inhibiting bone resorption and limiting oxidative stress. (2) Melatonin, as a promoter of bone formation, plays a role in promoting osseointegration and preventing peri-implantitis in oral implants. (3) More research is needed in the future to completely reveal the osteogenic mechanisms of melatonin and to make guidelines for optimal administration conditions and safety of melatonin in osseointegration and peri-implantitis. 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 important role of the nervous system in regulating wound repair and scar healing Song Jiamei, Liu Tingting, Yao Bin 2025, 29 (18):  3877-3884.  doi: 10.12307/2025.657 Abstract ( 234 )   PDF (1610KB) ( 140 )   Save BACKGROUND: Skin wound repair is an extremely complex process. The nervous system plays an important role in regulating wound repair and scar healing. OBJECTIVE: To review the role of the nervous system in the process of skin wound repair, including the roles of related factors and various cells in the repair of skin injury.  METHODS: The PubMed and CNKI databases were searched with the key words of “skin wound healing, nervous system, nerve regeneration, growth factor” in English and “skin wound healing, skin innervation, neuropeptide, growth factor, cell synergy” in Chinese. The time range of literature search was from 2003 to 2024, and 83 documents were finally included and analyzed. RESULTS AND CONCLUSION: (1) The skin is densely innervated by autonomic and sensory nerves, and there is growing evidence that the cutaneous nervous system is not only responsible for transmitting sensory information to the central nervous system, but also plays an important role in a variety of skin functions, including wound healing. (2) The nervous system acts on different stages of skin wound healing, which can regulate revascularization, promote the release of related growth factors and neurotransmitters, and cooperate with different types of cells to promote skin wound healing. Therefore, research on the underlying mechanisms of the nervous system has become a powerful target to promote skin wound healing. 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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Regulatory mechanisms and therapeutic strategies for cellular autophagy after spinal cord injury Yang Yike, Ren Yafeng, Li Bing, Shang Wenya, Huang Jing, Guo Jia, Liu Huiyao 2025, 29 (18):  3885-3896.  doi: 10.12307/2025.658 Abstract ( 171 )   PDF (1385KB) ( 174 )   Save BACKGROUND: Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway, which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury, and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction. OBJECTIVE: To summarize the role of cellular autophagy in spinal cord injury, related regulatory mechanisms of cellular autophagy and therapeutic strategies. METHODS: PubMed and CNKI databases were searched with the search terms of “spinal cord injury, autophagy, regulatory mechanisms, autophagy pathway, therapeutic target” in English and Chinese, respectively. A total of 133 English and 4 Chinese articles were included for review. RESULTS AND CONCLUSION: (1) Autophagy, a form of programmed cell death, has been shown to play a crucial role in the progression and treatment of spinal cord injury. Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis. A few studies have reported that excessive activation of autophagy, on the contrary, impedes neurological recovery following spinal cord injury. (2) After spinal cord injury, PI3K/AKT/mTOR, MAPK, AMPK and p53 signaling pathways, and factors such as Beclin-1, ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner. (3) Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury. And the drugs amlodipine, metformin, and minocycline, the Chinese medicines hawthorn leaf total flavonoids, betulinic acid, oxidized ginseng saponins, acupuncture, and extracellular vesicles of different cellular origins, exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy, while the drugs insulin-like growth factor 1 and eladavone, Chinese medicine ginseng saponin, acupuncture, and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy. (4) The related regulators of cellular autophagy are interconnected, and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy. (5) Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models, but there are no autophagy-related drugs used in the clinical practice, and their safety and efficacy need to be further investigated in the clinical field.   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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Irisin: a new link between exercise, disease and health Dong Zhengqin, Zheng Qi, Wu Guanmao, Wang Wenna, Chen Leqin 2025, 29 (18):  3897-3905.  doi: 10.12307/2025.668 Abstract ( 224 )   PDF (1668KB) ( 266 )   Save BACKGROUND: Irisin plays a crucial role in the physiological regulation of the body, advancing the browning process of white adipose tissue cells and exerting significant effects on the regulation of energy metabolism, thermogenesis, reduction of oxidative stress, and body mass loss. OBJECTIVE: To summarize the latest research progress in irisin and related diseases. METHODS: A computerized search of PubMed, MedReading, Web of Science, CNKI, WanFang, and VIP was performed to collect studies on the effect of irisin on relevant diseases. The search time was from January 1, 2011 to April 13, 2024. The search terms were “irisin, physical exercise, FNDC5, disease” in Chinese and English. According to the inclusion and exclusion criteria, 71 papers were finally included for review. RESULTS AND CONCLUSION: Irisin has important roles in anti-inflammation, fat metabolism, bone metabolism, brain health, cancer, diabetes, cardiovascular disease and kidney disease. Moreover, exercise can promote the expression of irisin, and different forms of exercises have different effects on irisin levels. Acute exercise, long-term exercise, resistance exercise and high-intensity exercise can all enhance irisin levels. The discovery of irisin provides a new potential basis for exercise therapy, which is a promising therapeutic target due to the multiple biological functions of irisin, and shows potential therapeutic value in the treatment of human metabolic diseases and their complications, obesity, and cancer. Irisin has a promising application as a potential target for the treatment of obesity, cognitive function, cardiovascular, cancer and other diseases in clinical practice. However, its specific mechanism of action still needs to be studied in depth, and there may be side effects. In the future, an in-depth understanding of the mechanism of irisin is needed to provide a more adequate basis for the treatment of obesity, cognitive dysfunction, cardiovascular disease, and cancer. 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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AMP-activated protein kinase mediates macrophage fatty acid oxidation: an approach to prevent and treat atherosclerosis with traditional Chinese medicine Cao Panxia, Peng Zining, Liu Shanshan, Fei Tiantian, Liang Tengyun, Zhang Mengwen, Wu Hong 2025, 29 (18):  3906-3914.  doi: 10.12307/2025.655 Abstract ( 153 )   PDF (1664KB) ( 302 )   Save BACKGROUND: The energy metabolism and polarization state of macrophages play a crucial role in the progression of atherosclerosis. Traditional Chinese Medicine (TCM) has shown significant therapeutic potential for prevention and treatment of atherosclerosis by regulating macrophage metabolic pathways. OBJECTIVE: To review the research progress in AMP-activated protein kinase regulation of macrophage energy metabolism and polarization and explore the mechanism of TCM in the prevention and treatment of atherosclerosis. METHODS: A computerized search was conducted on the databases including Web of Science, PubMed, and CNKI, covering relevant literature up to June 2024. The search terms were “AMPK, fatty acid oxidation, macrophage polarization, Traditional Chinese Medicine, atherosclerosis, coronary heart disease” in Chinese and English. A total of 62 articles were finally included for review. RESULTS AND CONCLUSION: The shift in macrophage energy metabolism from oxidative phosphorylation to glycolysis plays a key role in the progression of atherosclerosis. The activation of AMP-activated protein kinase in macrophages promotes fatty acid oxidation and M2 polarization, exerting anti-inflammatory effects and stabilizing arterial plaques. TCM monomers (such as ginseng, astragalus, and polygonatum) and compounds (such as Huanglian Jiedu Decoction, Yangxin Shumai Granules, and Tiaogan Daozhuo Formula) influence macrophage metabolism and cellular function by regulating the AMP-activated protein kinase pathway and intervening in multiple signaling pathways, such as nuclear factor-κB, peroxisome proliferator-activated receptor γ, and mammalian target of rapamycin, thereby achieving therapeutic effects. Future research should focus on the interactions between AMP-activated protein kinase, metabolism, and polarization pathways, as well as how TCM exerts its therapeutic effects through these pathways, providing new strategies for the treatment of atherosclerosis. 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 alpha7 nicotinic acetylcholine receptor and Alzheimer’s disease Zhang Songjiang, Li Longyang, Zhou Chunguang 2025, 29 (18):  3915-3924.  doi: 10.12307/2025.675 Abstract ( 219 )   PDF (1401KB) ( 675 )   Save BACKGROUND: The α7 nicotinic acetylcholine receptor is highly expressed in the cerebral cortex and hippocampus, and has been shown to play an important regulatory role in the pathological development of Alzheimer’s disease, making it a potential therapeutic target for Alzheimer’s disease. OBJECTIVE: To summarize the close relationship and interaction mechanism between α7 nicotinic acetylcholine receptor and Alzheimer’s disease. METHODS: Retrieve relevant literature was searched in CNKI and PubMed databases using the search terms of “alpha7 nicotinic acetylcholine receptor, Alzheimer’s disease, beta amyloid protein, agonist, positive allosteric modulator, antagonist” in Chinese and English, respectively. The search time was from database inception to July 2024. According to the inclusion criteria, the search results were accepted or excluded, and ultimately 83 articles that met the criteria were included for review. RESULTS AND CONCLUSION: The α7 nicotinic acetylcholine receptor interacts with β-amyloid protein to reduce the neurotoxicity of β-amyloid protein, such as promoting synaptic plasticity and rapid transmission of cholinergic synapses in Alzheimer’s disease, alleviating central nervous system inflammation induced by β-amyloid protein, resisting neuronal apoptosis, and thus having a protective effect on the brain of patients with Alzheimer’s disease. The α7 nicotinic acetylcholine receptor has great potential as a therapeutic target for Alzheimer’s disease, but there are still a series of issues that need to be addressed, such as desensitization of α7 nicotinic acetylcholine receptor, stability of moderate activity, and gene polymorphism. Screening for drugs with high specificity, safety and multi-target binding action centered on the α7 nicotinic acetylcholine receptor will be a future direction for the treatment of Alzheimer’s disease. 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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Efficacy of rehabilitation robots on lower limb motor function in patients with cerebral palsy: a Meta-analysis Liu Xingzhao, Hu Tong, Ma Yan, Wang Qian, Wei Xiaohui, Chang Wanpeng, Yu Shaohong 2025, 29 (18):  3925-3933.  doi: 10.12307/2025.654 Abstract ( 209 )   PDF (2140KB) ( 75 )   Save OBJECTIVE: To systematically evaluate the clinical effectiveness of rehabilitation robots in treating lower limb motor dysfunction in patients with cerebral palsy, and to compare the differences in therapeutic effects among different robots. METHODS: PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and WanFang databases were searched to collect randomized controlled trials on rehabilitation robotics for the treatment of motor dysfunction in patients with cerebral palsy, published from database inception to April 10, 2024. The main outcome indicators included muscle strength, muscle tension, balance function, step speed, step frequency, step length, walking endurance, lower limb motor function, and activities of daily living. The above indicators were coded according to the International Classification of Functioning, Disability and Health. Meta-analysis was performed to evaluate the clinical efficacy and compare the therapeutic efficacy of different rehabilitation robots. Literature search and screening were performed by two researchers, and the quality of the included literature was evaluated using the Cochrane 5.1.0 risk of bias assessment tool. Meta-analysis was performed using RevMan 5.4 software and Stata 16.0 software. RESULTS: (1) Fifteen articles were finally included, involving 512 patients with 260 in the experimental group and 252 in the control group. (2) The Meta-analysis results showed that rehabilitation robots could improve body structure and function [standardized mean difference=0.41, 95% confidence interval (CI): 0.24-0.58, P < 0.05], activities (standardized mean difference=0.53, 95% CI: 0.41-0.65, P < 0.05) and participation ability (mean difference=7.86, 95% CI: 1.54-14.18, P < 0.05). In particular, the rehabilitation robot improved lower limb muscle strength, balance function, step speed, walking endurance, lower limb gross motor function, and activities of daily living in patients with cerebral palsy, but showed insignificant effects on step frequency, step length, and muscle tension.  (3) The network Meta-analysis results showed that: step speed: Innowalkpro > Gait Trainer > Lokomat > 3DCalt; 6-minute walk test score: Gait Trainer > Lokomat > Lokohelp > Innowalkro; Gross Motor Function Measure-88D score: Lokohelp > Lokomat > KidGo > Innowalkpro > 3DCalt; Gross Motor Function Measure-88E score: Lokomat > Lokohelp > KidGo > 3DCalt > Innowalkpro. CONCLUSION: Based on the International Classification of Functioning, Disability, and Health, rehabilitation robot training can improve the lower limb motor function and activities of daily living in patients with cerebral palsy. The Innowalkpro robot was more effective in improving step speed; the Gait trainer robot was more effective in improving 6-minute walk test scores; the Lokohelp robot was more effective in improving Gross Motor Function Measure-88D zone scores; and the Lokomat robot was more effective in improving Gross Motor Function Measure-88E zone scores. 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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Immune cells mediate the association between different lipids and knee osteoarthritis: a genome-wide association analysis of European individuals Huo Jiang, Ding Yu, Yuan Jie 2025, 29 (18):  3934-3940.  doi: 10.12307/2025.678 Abstract ( 154 )   PDF (1641KB) ( 107 )   Save BACKGROUND: Observational studies have found a dual effect of lipids and immune cells on osteoarthritis progression, but the exact mechanism of action is not yet clear. OBJECTIVE: To investigate whether the causal relationship between lipids and knee osteoarthritis is regulated by immune cells.  METHODS: 179 lipids were obtained from the Linda Ottensman database, 731 immune cell-associated single nucleotide polymorphisms were obtained from Open GWAS as instrumental variables, and genome-wide association data for knee osteoarthritis were obtained from the Osteoarthritis Genetics Consortium. First, we used a two-sample Mendelian randomization method to investigate the causal relationships between lipids and knee osteoarthritis, between immune cells and knee osteoarthritis, and between lipids and immune cells from a genetic perspective. In addition, Bayesian-weighted Mendelian randomization verified the causal relationship between lipids and knee osteoarthritis, and reverse Mendelian randomization and Steiger directionality test assessed the positive relationship. Second, sensitivity analyses were performed, including Cochran’s Q test to eliminate heterogeneity, MR-PRESSO global test and MR-Egger intercept to rule out horizontal pleiotropy, and leave-one-out method to assess the effect of individual single nucleotide polymorphism drivers on random estimates. Finally, the mediating effect of specific immune cell traits in the causal relationship between lipids and knee osteoarthritis was determined by a two-step Mendelian randomization method.  RESULTS AND CONCLUSION: The inverse variance weighting method and Bayesian-weighted algorithm together identified eight lipid species that were causally associated with knee osteoarthritis. The results of Cochran’s Q, MR-PRESSO, and MR-Egger intercept were not statistically significant (P < 0.05). Meanwhile, a total of three sets of mediated relationships were calculated, with the lowest mediation percentage of 11.85% and the highest of 45.48%. These findings indicate the level of immune cells plays a potential role in the regulatory process of lipids and knee osteoarthritis, which provides new perspectives for in-depth exploration of knee 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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Genetic causal relationship between gut microbiota and osteoporosis: analysis of 211 gut microbiota from the UK database Fang Zhijie, Ma Qiangping, Dong Wantao, Wu Junyuan, Lu Yunlin 2025, 29 (18):  3942-3947.  doi: 10.12307/2025.679 Abstract ( 177 )   PDF (2108KB) ( 107 )   Save BACKGROUND: Osteoporosis is defined as a chronic metabolic bone disease, and a large amount of evidence has shown that gut microbiota is involved in osteoporosis. However, the causal relationship between gut microbiota and osteoporosis is yet unclear.  OBJECTIVE: To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.  METHODS: Pooled statistics from the MiBioGen Consortium’s Genome-Wide Association Analysis (GWAS) of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used. Inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis. Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.  RESULTS AND CONCLUSION: The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis. Among them, the R7 genus of Christensenaceae (MR Egger: β=-0.007; IVW: β=-0.004, P=0.028), Coprococus 3 (MR Egger: β=-0.008; IVW: β=-0.003, P=0.046) and Trichospirillum (MR Egger: β=-0.009; IVW: β=-0.004, P=0.003) may be protective factors for osteoporosis, while Hotella (MR Egger: β=0.006; IVW: β=0.002, P=0.033) and Eubacterium oxyoxide (MR Egger: β=0.001; IVW: β=0.003, P=0.046) may be potential risk factors for osteoporosis. Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis, while R7 of Christensenaceae, Coprococcus 3 and Spirillum can reduce the risk of osteoporosis. Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups. 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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Association between plasma proteins and osteoporosis and identification of potential therapeutic targets: information analysis based on the UK Biobank database Zhu Kai, Liu Wanxin, Luo Haobing, Feng Shengyi, Wang Qiugen 2025, 29 (18):  3948-3960.  doi: 10.12307/2025.690 Abstract ( 199 )   PDF (5027KB) ( 244 )   Save BACKGROUND: Osteoporosis is a significant contributor to the global burden of disease and disability. Plasma proteins are involved in complex biological processes and play a crucial role in uncovering disease mechanisms and identifying potential therapeutic targets. Although existing studies have suggested an association between plasma proteins and osteoporosis, the causal nature of these associations is not fully clarified. Therefore, it is imperative to identify the causal proteins associated with osteoporosis and potential therapeutic targets for the amelioration and management of this condition using large-scale plasma protein data.  OBJECTIVE: To evaluate the causal relationship between plasma proteins and osteoporosis based on the UK Biobank database as source information using the two-sample Mendelian randomization.  METHODS: A total of 1 001 plasma protein-related genome-wide significant quantitative trait loci (P < 5×10-8) were obtained from the UK Biobank database and used as instrumental variables, with linkage disequilibrium excluded. Summary data on osteoporosis were collected from the FinnGen database, which included 438 872 individuals of European descent. The study was analyzed using inverse variance weighting, MR-Egger regression, weighted median, and several sensitivity analyses to ensure the robustness of the results. Further, a protein-protein interaction network was constructed, and Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to explore the functional relevance and potential mechanisms of plasma proteins.  RESULTS AND CONCLUSION: (1) The Mendelian randomization analysis using the inverse variance weighted method identified 50 plasma proteins that have causal associations with osteoporosis (P < 0.05). Among them, 20 plasma proteins, including chromosome 19 open reading frame 12 (odds ratio [OR]=0.610; 95% confidence interval [CI]: 0.483-0.769, P=2.967×10-5) and epidermal growth factor (EGF; OR=0.877; 95% CI: 0.770-0.999, P=0.049), might be associated with a reduced risk of osteoporosis. In contrast, 30 plasma proteins, such as C-C motif chemokine ligand (CCL) 18 (OR=1.091; 95% CI: 1.037-1.147, P=0.001) and CD209 (OR=1.036; 95% CI: 1.003-1.070, P=0.034), might be associated with an increased risk of osteoporosis. After Bonferroni correction, only chromosome 19 open reading frame 12 showed a significant causal association with osteoporosis. (2) Multiple sensitivity analyses revealed no evidence of pleiotropy or heterogeneity, indicating the robustness of the results. (3) The construction of the PPI network identified core proteins such as EGF, CCL5, C-X-C motif chemokine ligand (CXCL) 13, CXCL5, vascular endothelial growth factor C, CCL17, CCL18, TEK receptor tyrosine kinase, tyrosine kinase with immunoglobulin like and EGF like domains 1, and CCL23. (4) Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that these plasma proteins play essential roles in the immune system, influencing osteoporosis through processes such as signal transduction, cell migration, and chemotaxis. (5) This study reveals the potential causal associations between 1 001 plasma proteins and osteoporosis, highlighting the utility of a large-scale, data-driven approach to identify new biomarkers and drug targets in diverse populations. Additionally, our findings suggest that processes such as immune signaling, cell migration, and chemotaxis play significant roles in the pathogenesis of osteoporosis, offering new directions for research under specific genetic backgrounds and environmental factors. Finally, the core proteins identified in this study (e.g., EGF, CCL5, and CXCL13) may serve as novel biomarkers or therapeutic targets, providing a new basis for the precise prevention and treatment of 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