• Junlong Zhong, Bin Wang, Biao Wu, Jie Shang, Ning Jiang, Aiyong Cui, Yufeng Chen, Xianghe Xu, and Huading Lu.
• Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
• Life Sci. 2021 Mar 15; 269: 119036.

AimsArticular cartilage degeneration has been recognized as the primary pathological change in osteoarthritis (OA). Mechanisms that govern the shift from cartilage homeostasis to OA remain unknown. Previous studies have reported that intrinsic circadian clock in chondrocytes could function to optimize cartilage repair/remodeling to optimum times of day, but little is known about its molecular mechanisms. This study attempted to investigate the potential role and mechanism of circadian gene Clock in OA pathology.Materials And MethodsThe expression of Clock in OA chondrocytes and cartilage was detected by qRT-PCR, western blot and immunohistochemistry. Temporal gene expression changes were analyzed using qRT-PCR in chondrocytes transfected with siClock following dexamethasone synchronization. In addition, the effect of Clock knockdown on senescent phenotypes and autophagic flux was evaluated in chondrocytes treated with siClock or siCntrl.Key FindingsThe expression of Clock was up-regulated in OA cartilage from humans and mouse models. Clock knockdown had no influence on rhythmic expression of the downstream genes in primary chondrocytes. We also found that Clock knockdown elevated antioxidant enzyme activities, diminished reactive oxygen species (ROS) production and attenuated senescence of chondrocytes via restoring autophagic flux.SignificanceClock knockdown can attenuate ROS-mediated senescence of chondrocytes through restoring autophagic flux in non-circadian manner, providing a potential therapeutic target for OA.Copyright © 2021 Elsevier Inc. All rights reserved.

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