细胞衰老在骨代谢及退行性疾病中的研究进展

Research progress of cellular senescence in bone metabolism and degenerative diseases

细胞衰老指细胞发生的不可逆的细胞周期停滞过程,是近年来疾病研究中的热点。细胞衰老的主要原因是DNA损伤或表观遗传学改变引起的抑癌基因p16,p21或p53的激活,从而导致细胞周期停滞。部分发生细胞衰老的细胞还具有衰老相关的分泌表型(SASP),通过分泌炎症因子以及细胞外基质水解酶引起组织微环境和周围细胞的变化。近年的研究显示,细胞衰老在维持骨发育稳态以及介导老年性骨关节疾病中具有重要功能,而衰老细胞的清除有助于延缓退行性骨关节疾病的进展。通过回顾近几年关于细胞衰老和SASP在骨组织中的研究,本文总结了在不同生理阶段骨组织发生细胞衰老的有益和不利作用,讨论了细胞衰老在老年退行性骨关节疾病中的作用。虽然相关研究已取得一定的进展,但仍存在研究干扰因素较多、相关机制研究较少等不足。而对细胞衰老影响骨发育及相关疾病的文献进行综述,有利于进一步理解细胞衰老的分子机制,为从细胞衰老的角度理解骨发育及防治退行性骨关节疾病提供理论基础和思路。

Cellular senescence refers to the irreversible cell cycle arrest process of cells,which is one of the focus in disease research in recent years.The main cause of cellular senescence is the activation of the tumor suppressor gene p16,p21 or p53 caused by DNA damage or epigenetic changes,resulting in growth arrest and the senescence‐associated secretory phenotype,which leads to the release of inflammatory factors and extracellular matrix degradation proteases or hydrolases.Evidences have indicated that cellular senescence is important in maintaining normal embryonic development and mediating bone diseases in ag-ing.Studies have shown that the clearance of senescence cells help delay the progression of age-related dis-eases in bone such as osteoarthritis and osteoporosis.Here,we reviewed recent studies on cellular senescence and SASP,and summarized the literature on the beneficial and adverse role of cellular senescence in different physiological stages.We also discussed the role of cellular senescence in maintaining the homeostasis of mus-culoskeletal system and mediating age-related degenerative bone and joint disorders.Although research on cellular senescence has made some progress,there are still some limitations.The purpose of this literature re-view is to provide a general picture on cellular senescence on bone development and bone-related diseases and to further facilitate understanding of the molecular mechanism of cell senescence and provide theoretical basis and ideas for understanding bone development as well as preventing degenerative bone and joint diseas-es from the cellular senescence perspective.