AMPK在骨关节炎发生发展中的作用

The roles of AMPK in the development and pathogenesis of osteoarthritis

骨关节炎(osteoarthritis,OA)是一种老年人最为常见的慢性关节疾病,其主要特征表现为关节软骨退行性变,但确切发病机制仍不十分清楚。腺苷酸激活蛋白激酶(AMPK)被称为细胞"能量感受器",是在细胞和整体水平上维持能量稳态的重要蛋白激酶。近来研究发现AMPK可通过调节关节软骨细胞内过氧化物酶体增殖物激活受体γ辅助活化因子1α(peroxisome proliferator-activated receptorγco-activator 1α,PGC-1α)、FOXO转录因子3a(forhead box O3a,FOXO3a)、核转录因子-κB(nuclear transcription factor-κB,NF-κB)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)等下游靶分子的活性而增强软骨细胞的抗应激能力,从而提高软骨细胞的生存能力。同时证实,当关节软骨细胞内AMPK活性下降时可导致关节软骨的退行性变从而引发骨关节炎。并且,也证实AMPK激动剂可延缓实验性骨关节炎的发生发展。本文将对此加以综述,以期为骨关节炎的治疗提供新靶点。

Osteoarthritis （OA）, the most common chronic joint disease in the elderly population, is mainly characterized by the degeneration of articular cartilage. However, its precise mechanisms are still not completely understood. 5＇-adenosine monophosphate-activated protein kinase （AMPK）, as a bioenergy sensor, is a critical protein kinase in maintaining energy homeostasis at both cellular and whole-body levels. Recent studies highlight a novel protective role for AMPK in chondrocyte survival which may be mediated via regulation of its downstream mediators including peroxisome proliferator-activated receptor γ co-activator 1 α（PGC- 1 α）, Forhead box O3a （FOXO3a）, nuclear transcription factor-κB（NF-κB）C/EBP homologous protein （CHOP）, mammalian target of rapamycin （mTOR）, etc. And it is also proved that decreased AMPK activity could contribute to the progression of OA by disrupting cartilage homeostasis. Indeed, current evidence indicates that AMPK activators may delay the development of experiment OA. In this review article, we will discuss the roles of AMPK in maintaining chondrocyte function and its potential to be used as new therapeutic target for OA.