破骨细胞分化机制的研究进展

The advance in the study of the mechanism of osteoclast differentiation

破骨细胞为人体主要的骨吸收细胞,对骨骼的发育及维持具有重要作用,同时破骨细胞的异常活化对多种溶骨性疾病的发展具有重要作用;明确破骨细胞的分化机制,可为多种骨代谢性疾病提供新的治疗策略及药物靶点。大量的实验对破骨细胞的分化机制进行了研究,并确认有一些基因为破骨细胞分化形成所必需,这些基因的缺失或突变将导致破骨细胞形成障碍,进而引起骨质硬化;并且由巨噬细胞集落刺激因子(macrophage colony stimulating factor,M-CSF)、核因子κB受体活化因子配体(receptor Activator for Nuclear Factor-κB Ligand,RANKL)及免疫受体酪氨酸激活基序(immunoreceptor tyrosine-based activation motif,ITAM)介导的3条重要的信号通路参与其分化过程,3条信号通路相互作用,共同促进破骨细胞的分化形成,但RANKL如何激活ITAM信号通路,有待进一步研究,本文就破骨细胞分化机制的研究进展作一综述。

Osteoclasts arethesoleboneresorbing cells. Thesecells areimportant for thedevelopment and maintenanceof thebone,and theabnormal activation of osteoclasts plays an important rolein thedevelopment of a variety of osteolytic diseases. Theclear understanding of themechanism of osteoclast differentiation may providenewtherapeutic strategies and novel drug targets for a variety of bonemetabolic diseases. A largenumber of experiments havebeen doneto study themechanism of osteoclast differentiation. Somegenes arerequired for theosteoclast differentiation. Threevital signal pathways mediated by M-CSF（ macrophagecolony stimulating factor,M-CSF）,RANKL（ receptor activator for nuclear factor-κB ligand,RANKL）,and ITAM（ immunoreceptor tyrosine-based activation motif,ITAM）,respectively,areinvolved in thedifferentiation process. To promotetheformation of osteoclast,thethreesignaling pathways interact with each other,but howRANKL activates theITAMsignaling pathway needs to befurther studied. This articlereviews theadvancein thestudy of mechanism of osteoclast differentiation.