OPG/RANKL/RANK信号通路在运动与骨免疫学中的研究进展

Research progress of OPG/RANKL/RANK signal pathway in exercise and osteoimmunology

自Arron在Nature上首次提出"骨免疫学"的概念以来,关于免疫系统与骨骼系统的研究逐渐成为国内外学者研究的热点。在骨免疫学研究中,OPG/RANKL/RANK信号通路作为免疫系统参与骨代谢调节的主要通路一直备受关注。当机体运动时,运动所产生的机械应力以及运动诱导的免疫功能变化均能通过OPG/RANKL/RANK信号通路影响骨代谢。适宜的运动能上调OPG基因表达,抑制RANKL分泌及其基因表达,促进IL-2、IL-18、IFN等保护性免疫细胞因子的分泌,有助于骨形成,使骨代谢趋向正平衡。而长时间大强度运动以及过度训练则上调RANKL基因表达,下调OPG基因表达,促使破骨细胞活性增强,同时又诱导IL-6、TNF、IL-17等炎症性细胞因子分泌增多,间接促进骨吸收,使骨代谢趋向负平衡。为了更深入地了解运动、免疫以及骨代谢之间的关系,本文综述了国内外关于运动、免疫与骨代谢的报道,旨在探讨运动对骨代谢及OPG/RANKL/RANK信号通路的调节机制以及运动应激下免疫细胞因子对OPG/RANKL/RANK信号通路的影响,为运动与骨免疫学的研究及骨代谢疾病的预防提供理论基础。

Since Arron first introduced the concept of osteoimmunology in Nature,the study of the immune system and skeletal system gradually has become a hot point nationally and internationally. In osteoimmunology,OPG / RANKL / RANK as a main signaling pathway involved in immune regulation of bone metabolism has drawn much attention. During body exercise,mechanical stress and changes of immune function can affect bone metabolism through OPG / RANKL / RANK signaling pathway. Moderate exercise can increase gene expression of OPG,inhibit secretion and gene expression of RANKL,and promote secretion of protective cytokines such as IL-2,IL-18,IFN,etc.,which benefits bone formation and positive balance of bone metabolism. Strenuous longtime exercise and excessive training increase gene expression of RANKL,inhibit gene expression of OPG,improve osteoclast activity,and promote secretion of inflammatory cytokines such as IL-6, TNF, and IL-17, which promote bone absorption indirectly,leading to negative balance of bone metabolism. In order to knowmore about the relationship between exercise,immune,and bone metabolism,this article summarizes the related reports about exercise,immune,and bone metabolism,explores the regulatory mechanism that exercise affects bone metabolism and OPG / RANKL / RANK signaling pathways and the effect of immunological cytokines on OPG / RANKL / RANK signaling pathways when doing exercise,and provides the theoretical foundation for exercise and osteoimmunology research and the prevention of bone metabolic diseases.