成骨信号通路在非创伤性股骨头坏死中的作用

Role of osteogenic signaling pathway in non-traumatic femoral head necrosis
Xu Canhong1, Chen Yueping2, Zhang Xiaoyun2 (1Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region, China; 2Department of Traumatic Orthopedics and Hand Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China)
摘要 背景：近年来非创伤股骨头坏死的发病率逐年增高，具有起病隐秘、病情发展迅速、致残率高的特点，给 患者及其家庭乃至社会带来极大的负担。若能明确其发病机制，对非创伤股骨头坏死的早期有效治疗有重 要意义。 目的：综述国内外相关文献，总结成骨信号通路在非创伤性股骨头坏死发病机制中的研究进展。 方法：以“非创伤性股骨头坏死，成骨，信号通路，发病机制”或“non-traumatic osteonecrosis of femoral head，Osteogenesis，Signaling pathways，pathogenesis，Wnt/β-catenin，PPARγ，TGF-β/Smad， PI3K/AKT，MAPK，Notch”等作为检索词，检索 PubMed、Embase、Medline、中国知网、万方、维普 等数据库中有关非创伤性股骨头坏死相关成骨信号通路机制及应用的研究文献。 结果与结论：近年来，成骨信号通路在非创伤性股骨头坏死中的作用日益受到重视，非创伤性股骨头坏死 发生发展中骨髓间充质干细胞的异常分化亦成为研究的焦点。成骨信号通路转导异常造成的骨髓间充质干 细胞异常分化、成骨分化抑制、骨质破坏增加、骨代谢平衡破坏，可能是导致非创伤性股骨头坏死的主要 原因。将 Wnt/β-catenin、PPARγ、TGF-β/Smad、PI3K/AKT、MAPK、Notch 等成骨信号通路作为干预 非创伤性股骨头坏死的治疗靶点或许是一种可行的办法，尽管目前已有大量体外及动物实验研究证实成骨信 号通路可能具有调控骨髓间充质干细胞分化并逆转股骨头坏死的潜能，但其具体的作用机制尚未明确，且目 前相关临床应用研究仍较少，故探索成骨信号通路的作用机制、加快临床的应用研究将是未来研究的方向。 关键词： 非创伤性股骨头坏死；骨髓间充质干细胞；成骨分化；信号通路；Wnt/β-catenin；PPARγ；TGF-β/Smad； PI3K/AKT；MAPK；Notch 中图分类号：R459.9；R363；R-331
Abstract BACKGROUND: In recent years, the incidence of non-traumatic femoral head necrosis has increased gradually. It has the characteristics of insidious onset, rapid development of disease and high disability rate, bringing a great burden to patients, their families and society. Confirming its pathogenesis is of great significance for the early effective treatment of non-traumatic femoral head necrosis. OBJECTIVE: To review the relevant literature worldwide and to summarize the research progress of osteogenic signaling pathways in the pathogenesis of non-traumatic femoral head necrosis. METHODS: PubMed, Embase, Medline, CNKI, VIP and WanFang databases were retrieved with the keywords of “non-traumatic osteonecrosis of femoral head, osteogenesis, signaling pathways, pathogenesis, Wnt/β-catenin, PPARγ, TGF-β/Smad, PI3K/AKT, MAPK, Notch” in English and Chinese, respectively. The articles concerning mechanism and application of osteogenic signaling pathways associated with avascular necrosis of the femoral head were included. RESULTS AND CONCLUSION: Recently, the role of osteogenic signaling pathways in non-traumatic femoral head necrosis has received increasing attentions. The abnormal differentiation of bone marrow mesenchymal stem cells in the development of non-traumatic femoral head necrosis has also become an issue of concern. Abnormal differentiation of bone marrow mesenchymal stem cells, inhibition of osteogenic differentiation, increased bone destruction, and imbalance of bone metabolism may be the main cause of non-traumatic femoral head necrosis, and Wnt/β-catenin, PPARγ, TGF-β/Smad, PI3K/AKT, MAPK, Notch and other osteogenic signaling pathways may be a viable approach to intervention for non-traumatic femoral head necrosis. Although a large number of in vitro and animal studies have confirmed that osteogenic signaling pathway may have the potential to regulate bone marrow mesenchymal stem cell differentiation and reverse femoral head necrosis, its specific mechanism of action remains unclear and little is reported on its clinical applications. Therefore, exploring the mechanism of signaling pathways and accelerating its clinical use are the directions of the future research. Key words: non-traumatic osteonecrosis of femoral head; bone marrow mesenchymal stem cells; osteogenesis; signaling pathways; Wnt/β-catenin; PPARγ; TGF-β/Smad; PI3K/AKT; MAPK; Notch Funding: the National Natural Science Foundation of China, No. 81760796 (to CYP); the Natural Science Foundation of Guangxi Zhuang Autonomous Region, No. 2015GXNSFAA139136 (to CYP); the Key Project of Health Department of Guangxi Zhuang Autonomous Region, No. S201419-05 (to CYP); the Basic Ability Enhancement Project of Young Teachers in Guangxi Colleges and Universities, No. 2019KY0352 and KY2016YB204 (both to ZXY); the Ten Programs of Traditional Chinese Medicine Development, No. (2018)1 (to ZXY [project participant]); the Qihuang Engineering Breeding Project of Guangxi University of Chinese Medicine, No. 030030001-04131804804-500101 (to ZXY [project participant]); the Graduate Education Innovation Program of Guangxi University of Chinese Medicine in 2019, No. YCSY201900106 (to XCH)