Wang Junjie, Li Jiali, Song Deye, Ni Jiangdong, Ding Muliang, Huang Jun, Yan Mingming
Department of Orthopaedic Surgery, The Second Xiangya Hospital of Central South University Changsha 410011, Hunan, China.
Department of Rheumatology and Nephrology, University of South China Affiliated Changsha Central Hospital Changsha 410008, Hunan, China.
Am J Transl Res. 2020 Dec 15;12(12):7670-7681. eCollection 2020.
Osteoarthritis (OA) is the most common skeletal disease and the leading cause of pain and disability in the aged population (>65 years). However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in failure to identify disease-modifying OA drugs. Altered metabolism has been shown to be a prominent pathological change in OA. As a critical bioenergy sensor, AMP-activated protein kinase (AMPK) mediates not only energy homeostasis but also redox balance in chondrocytes to counter various cell stress. Dysfunction of AMPK activity has been associated with reduced autophagy, impaired mitochondrial function, excessive reactive oxygen species generation, and inflammation in joint tissue. These abnormalities ultimately trigger articular cartilage degeneration, synovial inflammation, and abnormal subchondral bone remodeling. This review focuses on recent findings describing the central role of AMPK in joint homeostasis and OA development. We also highlight current advances that target AMPK as a novel therapeutic strategy for OA prevention.
骨关节炎（OA）是最常见的骨骼疾病，也是老年人群（>65岁）疼痛和残疾的主要原因。然而，OA发病机制中涉及的潜在因素仍然难以捉摸，这导致未能识别出改善病情的OA药物。代谢改变已被证明是OA的一个突出病理变化。作为一种关键的生物能量传感器，AMP激活的蛋白激酶（AMPK）不仅介导能量稳态，还介导软骨细胞中的氧化还原平衡，以应对各种细胞应激。AMPK活性功能障碍与自噬减少、线粒体功能受损、活性氧过度产生以及关节组织炎症有关。这些异常最终引发关节软骨退变、滑膜炎和软骨下骨异常重塑。本综述重点关注描述AMPK在关节稳态和OA发展中的核心作用的最新研究结果。我们还强调了将AMPK作为OA预防新治疗策略的当前进展。
