调控成骨细胞分化及骨形成关键信号通路的研究进展

调控成骨细胞分化及骨形成关键信号通路的研究进展

徐练孔清泉

【摘 要】目的综述在成骨细胞分化及骨形成过程中起关键调节作用的相关信号通路作用机制及研究进展。方法查阅近年来与成骨细胞分化及骨形成信号通路相关的文献，并进行综合分析。结果目前已发现多条信号通路参与了成骨细胞分化及骨形成的调节，其中BMP-Smads、Wnt/β-catenin、Notch、Hedgehog、FGF信号通路的作用最关键。这些信号通路不但自身具有较复杂的调控机制，而且彼此相互联系、相互影响，从而组成了一个更复杂而精细的调控网络，共同参与成骨细胞分化及骨形成的调节。然而，由于相关动物实验技术不成熟，临床试验研究较少，其详细作用机制体系仍不十分明了。结论对成骨相关信号通路的进一步深入研究，将有望彻底揭开成骨细胞分化及骨形成过程的完整分子机制，从而为临床有效防治成骨分化及骨形成异常性疾病提供理论依据。

【关键词】 MSCs成骨细胞分化 骨形成 信号通路

RESEARCH PROGRESS OF KEY SIGNALING PATHWAYS IN OSTEOBLAST DIFFERENTIATION AND BONE FORMATION REGULATION/XU Lian, KONG Qingquan. Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China. Corresponding author: KONG Qingquan, E-mail: kqqspine@ 【Abstract】Objective To review the mechanism and research progress of signaling pathways which play key roles in the regulation of osteoblast diff erentiation and bone formation. Methods Recent articles about signaling pathways of osteoblast diff erentiation and bone formation were reviewed and comprehensively analyzed. Results At present, multiple signaling pathways have been found to be involved in the regulation of osteoblast diff erentiation and bone formation, among which bone morphogenetic protein-Smads, Wnt/β-catenin, Notch, Hedgehog, and fi broblast growth factor signaling pathways may play the most important roles. Not only each pathway has a complex regulatory mechanism itself, but also contacts and impacts with each other, thus they formed a more complicated and sophisticated regulatory network, and regulate together osteoblast diff erentiation and bone formation. However, the mechanisms in detail of those pathways are still not very clear, because the animal experiment techniques are not yet mature as well as the relevant clinical trials were carried out not too much. Conclusion The complete molecular mechanism of osteoblast diff erentiation and bone formation should be further investigated, so as to lay a theory foundation for preventing and treating the common bone diseases in clinical which are involve in osteoblast diff erentiation and bone formation.

【Key words】 Mesenchymal stem cells Osteoblast diff erentiation Bone formation Signaling pathway Foundation item: National Natural Science Foundation of China (81171731)

成骨细胞是人体骨组织的重要组成成分，也是参与骨形成的主要功能细胞，在骨骼生长发育及骨量维持方面扮演着关键角色。它来源于具有多向分化潜能的MSCs，经细胞增殖、细胞外基质合成、成熟及矿化后最终发展成为骨细胞，从而促进骨形成及维持骨量。从分子生物学水平上看，目前已知多条信号通路参与了成骨细胞分化过程的调节，其中最重要的信号通路包括BMP-Smads、Wnt/β-连环蛋白（β-catenin）、Notch、Hedgehog、FGF等。这些信号通路在调控成骨

DOI：10.7507/1002-1892.20140321

基金项目：国家自然科学基金资助项目（81171731）

作者单位：四川大学华西医院骨科（成都，610041）

通讯作者：孔清泉，副教授，硕士生导师，研究方向：脊柱外科，E-mail: kqqspine@

网络出版时间：2014-10-21 17:16:33；网络出版地址：http://www. /kcms/detail/51.1372.R.20141021.1716.024.html 细胞分化及骨生成方面起着重要作用，一旦其中一条或数条信号通路调节受阻，都会引起成骨细胞分化异常或骨形成障碍，进而导致相应骨代谢疾病的发生，如骨质疏松症、骨硬化症等。因此，为了更好地认识和治疗这类疾患，阐明这些信号通路在调节成骨细胞分化及骨形成方面的作用机制及规律具有重要意义。现对成骨细胞分化及骨形成过程中起关键调节作用的信号通路的相关研究进展作一综述，为下一步研究奠定基础。

1概述

成骨细胞作为骨形成的主要功能细胞，在分化成熟过程中会逐步表达如ALP、骨钙素、血清Ⅰ型前胶原C端肽等特异性标志物。同时，在此过程中也会受到一系列转录因子的调控，如Runt相关转录因子