骨关节炎与线粒体异常

Osteoarthritis and mitochondrial abnormalities

背景:骨关节炎是一种与多种因素相关的慢性进行性的关节退行性疾病,而线粒体在其中发挥的作用不可忽视。目的:综述目前相关文献,总结线粒体与骨关节炎的关系,了解线粒体损伤在骨关节炎发病中的机制,为从线粒体途径治疗骨关节炎提供理论参考。方法:以“mitochondria;mitochondrial;osteoarthritis;ostarthritis;ostearthritis”为检索关键词,从PubMed数据库中以检索式“(mitochondria)OR(mitochondrial)AND(osteoarthritis)OR(ostarthritis)OR(ostearthritis)”检索。初检得到2000-2021年发表的文献455篇,按纳入排除标准最终共入选61篇文献进行综述。结果与结论:①线粒体在骨关节炎病变中发挥了关键性的作用,在骨关节炎病变中,线粒体氧化还原的异常会抑制基质合成、激活基质金属蛋白酶降解基质成分、诱导细胞因子产生和诱导软骨细胞凋亡,进而促进软骨退行性病变;生物发生的缺乏会导致软骨细胞前分解代谢反应的加速;动力学异常时受损的线粒体会积累,导致线粒体不能产生足够的生物能量,调节钙并维持氧化还原状态从而加速骨关节炎的发展;有丝分裂受损时功能失调的线粒体不能被及时清除从而导致线粒体动态平衡的紊乱;遗传学异常时会导致线粒体呼吸和糖酵解增加,自由基和促炎细胞因子产生增加,细胞凋亡程度上升从而导致软骨细胞功能障碍;而钙调节异常时会导致活性氧过度产生,线粒体去极化及线粒体膜电位降低,进而使软骨细胞凋亡。②在骨关节炎的治疗方面,以内源性AMPK、SIRT、Parkin为靶点的药物,以及外源性的抗氧化剂,能够抑制线粒体凋亡和增强线粒体动力学的药物有望成为早期治疗骨关节炎的潜在药物。

BACKGROUND:Osteoarthritis is a chronic and progressive joint degenerative disease associated with multiple factors,and the role of mitochondria in osteoarthritis should not be ignored.OBJECTIVE:To review the current relevant literature,summarize the relationship between mitochondria and osteoarthritis,understand the mechanism of mitochondrial damage in the pathogenesis of osteoarthritis,and provide theoretical reference for the treatment of osteoarthritis through mitochondrial pathway.METHODS:The key words were“mitochondria;mitochondrial;osteoarthritis;ostarthritis;ostearthritis”.The retrieval formula was“(mitochondria)OR(mitochondrial)AND(osteoarthritis)OR(ostarthritis)OR(ostearthritis)”on PubMed database.455 articles published from 2000 to 2021 were primarily retrieved.According to the inclusion and exclusion criteria,61 articles were finally included for review.RESULTS AND CONCLUSION:(1)Mitochondria play a key role in osteoarthritis.Abnormal mitochondrial REDOX can inhibit matrix synthesis,activate matrix metalloproteinase to degrade matrix components,induce cytokine production and chondrocyte apoptosis,and promote cartilage degeneration.Lack of biogenesis leads to accelerated prechondrocyte catabolism.When the kinetics is abnormal,damaged mitochondria accumulate,which leads to the inability of mitochondria to produce enough biological energy,regulate calcium and maintain a REDOX state,thereby accelerating the development of osteoarthritis.When mitosis is damaged,the dysfunctional mitochondria cannot be cleared in time,leading to the disorder of mitochondrial dynamic balance.Genetic abnormalities lead to increased mitochondrial respiration and glycolysis,increased production of free radicals and pro-inflammatory cytokines,and increased apoptosis resulting in chondrocyte dysfunction.However,abnormal calcium regulation will lead to excessive production of reactive oxygen species,mitochondrial depolarization and decreased mitochondrial membrane potential,which will lead to chondrocyte apoptosis.(2)In the treatment of osteoarthritis,drugs targeting endogenous AMPK,SIRT and Parkin,as well as exogenous antioxidants that can inhibit mitochondrial apoptosis and enhance mitochondrial dynamics are expected to become potential drugs for the early treatment of osteoarthritis.