中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (33): 8591-8606.doi: 10.12307/2026.477

• 骨组织构建 bone tissue construction • 上一篇    下一篇

姜黄素促进成骨分化治疗骨质疏松的机制

闫小龙1，赵灿斌2，邵  将3，孙宏章4，管东辉3，秦  英5，李晓阳3，陈东峰3   

  1. 1济南市长清区人民医院/山东中医药大学附属医院大学城医院骨科，山东省济南市   250300；2广西中医药大学第一临床医学院，广西壮族自治区南宁市   530200；3山东中医药大学附属医院骨科，山东省济南市   250014；4济南市章丘区中医医院骨科，山东省济南市   250200；5济南市长清区中医医院骨科，山东省济南市   250300
  • 收稿日期:2025-11-15 修回日期:2026-03-09 出版日期:2026-11-28 发布日期:2026-06-09
  • 通讯作者: 邵将，博士，主治医师，山东中医药大学附属医院骨科，山东省济南市 250014 共同通讯作者：孙宏章，硕士，医师，济南市章丘区中医医院骨科，山东省济南市 250200
  • 作者简介:闫小龙，男，1985年生，硕士，副主任医师，主要从事四肢骨盆髋臼骨折及脱位的手法复位及微创手术治疗，骨髓炎、骨折不愈合的中西医结合治疗。
  • 基金资助:
    山东省自然科学基金项目(ZR2022MH147)，项目负责人：管东辉

Mechanism by which curcumin promotes osteogenic differentiation in the treatment of osteoporosis

Yan Xiaolong1, Zhao Canbin2, Shao Jiang3, Sun Hongzhang4, Guan Donghui3, Qin Ying5, Li Xiaoyang3, Chen Dongfeng3   

  1. 1Orthopedics Department, University Town Hospital, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong Province, China; 2First Clinical Medical College, Guangxi University of Traditional Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China; 3Orthopedics Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; 4Orthopedics Department, Jinan Zhangqiu District Hospital of TCM, Jinan 250200, Shandong Province, China; 5Orthopedics Department, Changqing District Traditional Chinese Medicine Hospital, Jinan 250300, Shandong Province, China
  • Received:2025-11-15 Revised:2026-03-09 Online:2026-11-28 Published:2026-06-09
  • Contact: Shao Jiang, PhD, Attending physician, Orthopedics Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China Co-corresponding author: Sun Hongzhang, MS, Physician, Orthopedics Department, Jinan Zhangqiu District Hospital of TCM, Jinan 250200, Shandong Province, China
  • About author:Yan Xiaolong, MS, Associate chief physician, Orthopedics Department, University Town Hospital, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong Province, China
  • Supported by:
    Natural Science Foundation of Shandong Province, No. ZR2022MH147 (to GDH)

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摘要：



文题释义：
骨质疏松：是一种以骨量低下、骨微结构损坏为特征，导致骨脆性增加、易发生骨折的全身性骨代谢性疾病。骨质疏松发病与成骨细胞分化能力减弱、破骨细胞过度骨吸收相关，使骨重建平衡被打破，常见于老年人群及绝经后女性。
成骨分化：是成骨细胞逐步增殖、成熟并合成骨基质的过程，对维持骨代谢平衡至关重要。成骨细胞分化能力直接影响骨组织的重建与修复，成骨细胞功能受抑制是骨质疏松发生的关键病理环节。

背景：骨髓间充质干细胞成骨分化功能减弱是骨质疏松发生发展的关键病理环节。姜黄素可通过调控磷脂酰肌醇3激酶/蛋白激酶B信号通路促进成骨分化治疗骨质疏松，但具体作用机制尚未明确。
目的：研究姜黄素调控磷脂酰肌醇3激酶/蛋白激酶B信号通路促进成骨分化治疗骨质疏松的机制。
方法：通过网络药理学筛选姜黄素药物作用靶点及成骨分化、骨质疏松的相关靶点基因，三者取交集后，绘制蛋白质相互作用网络图并进行基因本体论、京都基因与基因组百科全书富集分析及分子对接处理。通过生物信息学筛选蛋白质相互作用网络中潜在的标志基因，构建临床预测模型；运用单细胞转录组学技术分析标志基因在成骨细胞谱系分群中的表达模式；最后进行细胞及动物实验验证。
结果与结论：①筛选出姜黄素的药物作用靶点366个，姜黄素与成骨分化及骨质疏松的交集靶点有134个；②京都基因与基因组百科全书富集分析显示，交集靶点涉及磷脂酰肌醇3激酶/蛋白激酶B信号通路；③分子对接显示姜黄素主要活性成分与磷脂酰肌醇3激酶/蛋白激酶B信号通路相关靶点均可良好对接；④由基因表达综合数据库下载骨质疏松相关基因集，将蛋白质相互作用网络图中的134个靶点基因通过113种机器学习的算法组合筛选得到14个潜在的标志基因，其中包括磷脂酰肌醇3激酶/蛋白激酶B信号通路的靶点基因PIK3R1、PIK3CG、GSK3β、AKT1，这14个基因可能在姜黄素促进成骨分化治疗骨质疏松方面发挥着重要作用；⑤单细胞转录组学分析显示骨质疏松患者的成骨细胞谱系分群中存在一群GSK3β高表达的细胞群，且该细胞分群可能与骨质疏松的发生发展密切相关；⑥拟时序分析发现在骨质疏松发展过程中GSK3β表达量逐渐升高，PIK3R1、PIK3CG、AKT1表达量逐渐降低；⑦细胞实验发现，敲除GSK3β后，促进了小鼠颅顶成骨前体细胞亚克隆14(MC3T3-E1 subclone 14 )的成骨分化，具体表现在碱性磷酸酶染色、茜素红染色着色加深；碱性磷酸酶活性以及钙盐沉积显著增加(P < 0.05)；β-catenin mRNA以及蛋白表达量显著升高(P < 0.05)；CCK-8与EdU结果显示，5，10 μmol/L姜黄素无明显毒性且可以明显促进MC3T3-E1 subclone 14细胞增殖；此外，5，10 μmol/L姜黄素干预后明显促进了MC3T3-E1 subclone 14细胞成骨分化；⑧动物实验显示，姜黄素通过增加骨小梁数量并改善骨小梁排列紊乱程度来改善去势卵巢大鼠股骨组织的骨质疏松情况；姜黄素干预后骨质疏松大鼠股骨远端骨组织中磷脂酰肌醇3激酶、蛋白激酶B1表达及磷酸化修饰水平显著升高(P < 0.05)，GSK3β磷酸化修饰水平显著下降(P < 0.05)，此外，c-MYC、Cyclin d1以及骨形态发生蛋白 2、骨钙素、骨桥蛋白及Osterix的表达显著升高(P < 0.05)。综上所述，磷脂酰肌醇3激酶/蛋白激酶B信号通路中的GSK3β表达升高可能是导致成骨分化功能下降及骨质疏松发生发展的关键因素，姜黄素通过激活磷脂酰肌醇3激酶/蛋白激酶B信号通路促进成骨分化来治疗骨质疏松。
https://orcid.org/0009-0009-3509-9673 (闫小龙) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 姜黄素, 成骨分化, 骨质疏松, 单细胞转录组学, 磷脂酰肌醇3激酶, 蛋白激酶B, 信号通路

Abstract: BACKGROUND: The diseased osteogenic differentiation function of bone marrow mesenchymal stem cells is a key pathological link in the occurrence and development of osteoporosis. Curcumin can promote osteogenic differentiation and treat osteoporosis by regulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, but the specific mechanism of action remains unclear.
OBJECTIVE: To investigate the mechanism by which curcumin regulates the phosphatidylinositol 3-kinase/protein kinase B signaling pathway to promote osteogenic differentiation for the treatment of osteoporosis. 
METHODS: Network pharmacology was used to screen the drug action targets of curcumin and target genes related to osteogenic differentiation and osteoporosis. The intersection targets of the three were used to construct a protein-protein interaction network diagram and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and molecular docking. Bioinformatics was used to screen potential signature genes in the protein-protein interaction network and construct a clinical prediction model. Single-cell transcriptomics technology was used to analyze the expression patterns of signature genes in osteoblast lineage subpopulations. Finally, cell and animal experiments were conducted for verification.
RESULTS AND CONCLUSION: (1) A total of 366 drug targets of curcumin were screened, and 134 intersection targets were identified among curcumin, osteogenic differentiation, and osteoporosis. (2) Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the intersection targets were involved in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. (3) Molecular docking showed that the main active components of curcumin could be well docked with the targets related to the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. (4) Osteoporosis-related gene sets were downloaded from the Gene Expression Omnibus database. The 134 target genes in the protein-protein interaction network were screened by 113 combinations of machine learning algorithms to obtain 14 potential signature genes, including target genes in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway: PIK3R1, PIK3CG, GSK3β, and AKT1. These 14 genes may play important roles in curcumin promoting osteogenic differentiation for the treatment of osteoporosis. (5) Single-cell transcriptomics analysis showed that there was a cell subpopulation with high GSK3β expression in the osteoblast lineage of osteoporosis patients, and this cell subpopulation might be closely related to the occurrence and development of osteoporosis. (6) Pseudotime analysis found that during the development of osteoporosis, the expression level of GSK3β gradually increased, while the expression levels of PIK3R1, PIK3CG, and AKT1 gradually decreased. (7) Cell experiments showed that after GSK3β knockout, the osteogenic differentiation of mouse MC3T3-E1 subclone 14 was promoted, as evidenced by deeper staining in alkaline phosphatase staining and Alizarin Red S staining, and significantly increased alkaline phosphatase activity and calcium deposition (P < 0.05). The mRNA and protein expression levels of β-catenin were significantly increased (P < 0.05). Cell counting kit-8 and EdU results showed that 5 and 10 μmol/L curcumin had no obvious toxicity and could significantly promote the proliferation of MC3T3-E1 subclone 14 cells. In addition, intervention with 5 and 10 μmol/L curcumin significantly promoted the osteogenic differentiation of MC3T3-E1 subclone 14. (8) Animal experiments showed that curcumin improved osteoporosis in the femoral tissue of ovariectomized rats by increasing the number of trabecular bones and ameliorating the disorder of trabecular bone arrangement. After curcumin intervention, the expression and phosphorylation levels of phosphatidylinositol 3-kinase and protein kinase B1 in the distal femoral bone tissue of osteoporotic rats were significantly increased (P < 0.05), and the phosphorylation level of GSK3β was significantly decreased (P < 0.05). In addition, the expression levels of c-MYC, Cyclin D1, bone morphogenetic protein 2, osteocalcin, osteopontin, and Osterix were significantly increased (P < 0.05). In conclusion, the increased expression of GSK3β in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway may be a key factor leading to the decline of osteogenic differentiation function and the occurrence and development of osteoporosis. Curcumin treats osteoporosis by activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway to promote osteogenic differentiation.

Key words: curcumin, osteogenic differentiation, osteoporosis, single-cell transcriptomics, phosphatidylinositol 3-kinase, protein kinase B, signaling pathway

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