Zhang Xin-Xin, He Shi-Hao, Liang Xu, Li Wei, Li Tian-Fang, Li Dai-Feng
Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Pharmacol. 2021 Aug 23;12:728100. doi: 10.3389/fphar.2021.728100. eCollection 2021.
Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. For a long time, OA has been considered as a degenerative disease, while recent observations indicate the mechanisms responsible for the pathogenesis of OA are multifaceted. Aging is a key factor in its development. Current treatments are palliative and no disease modifying anti-osteoarthritis drugs (DMOADs) are available. In addition to articular cartilage degradation, cellular senescence, synovial inflammation, and epigenetic alterations may all have a role in its formation. Accumulating data demonstrate a clear relationship between the senescence of articular chondrocytes and OA formation and progression. Inhibition of cell senescence may help identify new agents with the properties of DMOADs. Several anti-cellular senescence strategies have been proposed and these include sirtuin-activating compounds (STACs), senolytics, and senomorphics drugs. These agents may selectively remove senescent cells or ameliorate their harmful effects. The results from preclinical experiments and clinical trials are inspiring. However, more studies are warranted to confirm their efficacy, safety profiles and adverse effects of these agents.
骨关节炎（OA）是一种慢性、使人衰弱的关节疾病，其特征是关节软骨进行性破坏。长期以来，OA一直被认为是一种退行性疾病，而最近的观察表明，OA发病机制是多方面的。衰老在其发展过程中是一个关键因素。目前的治疗方法只是姑息性的，尚无疾病改善抗骨关节炎药物（DMOADs）。除了关节软骨降解外，细胞衰老、滑膜炎症和表观遗传改变可能都在其形成过程中起作用。越来越多的数据表明，关节软骨细胞衰老与OA的形成和进展之间存在明确的关系。抑制细胞衰老可能有助于识别具有DMOADs特性的新药物。已经提出了几种抗细胞衰老策略，其中包括沉默调节蛋白激活化合物（STACs）、衰老细胞溶解剂和衰老细胞形态调节剂。这些药物可以选择性地清除衰老细胞或减轻其有害影响。临床前实验和临床试验的结果令人鼓舞。然而，需要更多的研究来证实这些药物的疗效、安全性和不良反应。
