Merton College, University of Oxford, Oxford OX1 4JD, United Kingdom.
Merton College, University of Oxford, Oxford OX1 4JD, United Kingdom.
Exp Gerontol. 2021 Jan;143:111163. doi: 10.1016/j.exger.2020.111163. Epub 2020 Nov 20.
Osteoarthritis (OA) is a common and debilitating joint disease which develops and progresses with age. Despite extensive research into the disease, potent disease-modifying drugs remain elusive. Changes to the character and function of chondrocytes of the articular cartilage underly the pathogenesis of OA. A recently emerging facet of chondrocyte biology that has been implicated in OA pathogenesis is the role of circadian rhythms, and the cellular clock which governs rhythmic gene transcription. Here, we review the role of the chondrocyte's cellular clock in governing normal homeostasis, and explore the wide range of consequences that contribute to OA development when the clock is dysregulated by aging and other factors. Finally, we explore how harnessing this understanding of clock mechanics in aging and OA can be translated into novel treatment strategies, or 'chronotherapies', for patients.
骨关节炎(OA)是一种常见且使人虚弱的关节疾病,随着年龄的增长而发展和加重。尽管对该疾病进行了广泛的研究,但仍然难以找到有效的疾病修饰药物。关节软骨的软骨细胞的特征和功能的变化是 OA 发病机制的基础。最近,细胞生物学中一个新兴的方面与 OA 的发病机制有关,即昼夜节律,以及调节节律性基因转录的细胞时钟。在这里,我们回顾了软骨细胞的细胞时钟在维持正常动态平衡中的作用,并探讨了当时钟因衰老和其他因素而失调时,其对 OA 发展的广泛影响。最后,我们探讨了如何利用对衰老和 OA 中时钟机制的理解,将其转化为针对患者的新型治疗策略或“时间治疗”。