骨代谢信号通路的研究进展

Research progress in the signal pathways in bone metabolism

骨代谢包括骨形成及骨吸收两方面,受到多种因素的调控,其分子机制涉及遗传基因、信号通路、激素及旁分泌因子等多方面作用,而信号通路在其中起到了重要的调控作用。在目前的骨代谢信号通路研究中,BMP/Smads、Wnt/β-catenin及OPG/RANKL/RANK等3条通路已经得到较为深入的研究,并且公认为在骨代谢中起到了关键的信号调节作用,其中BMP/Smads及、Wnt/β-catenin通路主要影响骨形成,而OPG/RANKL/RANK则主要影响骨吸收。最新的研究表明,低氧/低氧诱导因子-la通路、PDGF、TGF-beta和FGF通路、AKt2选择通路、G蛋白信号通路、硫酸已酰肝素和硫酸软骨素通路、黏着斑激酶及胞外信号调节激酶通路等同样对成骨细胞及破骨细胞的分化增殖起到调节作用,并且发现BMP/Smads通路和Wnt/β-catenin通路之间存在着相互调节作用。对骨代谢信号通路的深入研究,可为骨代谢疾病尤其是骨质疏松症提供潜在的以细胞为基础的治疗新途径。

Bone metabolism consists of bone formation and bone resorption. It is regulated by various factors. At the molecular level, the multifunctional roles of genes, signaling pathways, hormones, and paracrine factors are involved in the regulation of bone metabolism. Among which, the signal pathways play an important role in this process. Currently, in the studies of the bone metabolic signal pathways, BMP/Smads, Wnt/β-catenin, and OPG/RANKL/RANK signal pathways have been deeply studied, and it is generally accepted as key signal pathways in the bone metabolism. BMP/Smads and Wnt/β-catenin pathways mainly affect bone formation, while OPG/RANKL/RANK pathway controls the process of bone resorption. The latest studies show that hypoxia/ hypoxia-inducible factor-la pathway, PDGF, TGF-β and FGF pathway, AKt2 pathway, G protein signaling pathway, heparin sulfate and chondroitin sulfate pathway, and focal adhesion kinase and extra-cellular signal-related kinase pathway also play regulating roles in the differentiation and proliferation of osteoblasts and osteoclasts. The interaction between BMP/Smads pathway and Wnt/[3-catenin pathway has also been found. Intensive study on bone metabolism pathway can help to find potential cell-based therapeutic ways for metabolic bone diseases especially for osteoporosis.