骨髓间充质干细胞向软骨及骨分化：Wnt5a/PCP信号通路作用的研究与进展

Bone marrow mesenchymal stem cells differentiate into cartilage and bone: roles of Wnt5a/PCP signaling pathways

背景:Wnt5a具有抑制经典Wnt信号和激活非经典Wnt信号途径的生物学功能。近年来,研究发现Wnt5a介导的Wnt5a/PCP非经典信号通路在骨髓间充质干细胞的增殖和分化过程中发挥着重要作用。但其参与骨髓间充质干细胞向软骨和骨分化形成的机制并不完全清楚。目的:综述Wnt5a/PCP信号通路中的相关下游效应分子,及其在骨髓间充质干细胞向软骨和骨分化形成过程中作用的最新研究进展。方法:以"间充质干细胞、Wnt信号通路、软骨分化、骨分化"为中文捡索词,以"BMSCs、Chondrogenic differentiation、Osteogenic differentiation、Wnt、Fzd、Ror2、Rho A、ROCK、JNK"为英文检索词,在维普、中国知网(CNKI)期刊全文数据库和Pub Med数据库检索2000年1月至2016年2月有关Wnt信号通路参与间充质干细胞向软骨及骨分化的文献。排除陈旧性和重复性研究,重点分析43篇文献进行综述。结果与结论:Wnt5a是非经典Wnt信号途径的代表性Wnt蛋白,主要通过其下游信号分子Fzd、Ror、Rho A、ROCK、JNK等介导,参与细胞骨架、细胞迁移和细胞极化等活动,从而调控其增殖和分化。然而Wnt5a/PCP信号通路在骨髓间充质干细胞向软骨和骨分化过程中具体的作用机制并不清楚,下游效应分子之间是如何协同或独立发挥作用也是未知的,这些问题均需要进一步深入研究。

BACKGROUND：Wnt5a is able to inhibit canonical Wnt signaling and activate non-canonical Wnt signaling pathway. In recent years, it has been found that non-classical Wnt5a/PCP signaling pathway mediated by Wnt5a plays an important role in the process of bone marrow mesenchymal stem cel proliferation and differentiation, but the underlying mechanism is unclear. OBJECTIVE：To summarize the progress in downstream effector molecules related to Wnt5a/PCP signaling pathway, and its roles in the chondrogenic and osteogenic differentiation of bone marrow mesenchymal stem cel s. METHODS：A computer-based online search of CqVip, CNKI and PubMed databases between January 2000 and February 2016 was performed using the Chinese keywords of“BMSCs, Wnt signaling pathways, chondrogenic differentiation, osteogenic differentiation”and English keywords of“BMSCs, chondrogenic differentiation, osteogenic differentiation, Wnt, Fzd, Ror2, RhoA, ROCK, JNK”, respectively. Literatures related to bone marrow mesenchymal stem cel chondrogenic and osteogenic differentiation were selected. Final y, 43 eligible articles were included for analysis through excluding the old and repeated research. RESULTS AND CONCLUSION：Wnt5a, a representative protein in non-canonical Wnt signaling pathway, paticipates in the cytoskeleton, cel migration and cel polarization and other activities by mediating its downstream signaling molecules such as Fzd, Ror, RhoA, ROCK, JNK, thereby regulating its proliferation and differentiation. But it is unclear how Wnt5a/PCP participates in the bone marrow mesenchymal stem cel chondrogenic and osteogenic differentiation and how the downstream effector molecules interact or function independently, which requires further studies.