Department of Bone and Joint Surgery, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, Guangdong, China.
Institute of Orthopedic Diseases & The Bone and Joint Disease institute of Guangdong-Hong Kong-Macao Greater Bay Area, Jinan University, Guangzhou, 510630, China.
Arthritis Res Ther. 2022 Feb 28;24(1):59. doi: 10.1186/s13075-022-02747-4.
Osteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole "organ" including cartilage, subchondral bone, synovium, and muscles. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the pathogenesis of age-related diseases including OA. In this review, we mainly focus on the role of the senescent skeletal cells (chondrocytes, osteoblasts, osteoclasts, osteocyte, and muscle cells) in initiating the development and progression of OA alone or through cross-talk with the macrophages/synovial cells. Accordingly, we summarize the current OA-targeted therapies based on the abovementioned theory, e.g., by eliminating senescent skeletal cells and/or inhibiting the senescence-associated secretory phenotype (SASP) that drives senescence. Furthermore, the existing animal models for the study of OA from the perspective of senescence are highlighted to fill the gap between basic research and clinical applications. Overall, in this review, we systematically assess the current understanding of cellular senescence in OA, which in turn might shed light on the stratified OA treatments.
骨关节炎（OA）已被认为是一种与年龄相关的退行性疾病，常见于老年人，影响整个“器官”，包括软骨、软骨下骨、滑膜和肌肉。越来越多的研究表明，局部关节中各种应激引起的衰老细胞的积累导致包括 OA 在内的与年龄相关疾病的发病机制。在这篇综述中，我们主要关注衰老的骨骼细胞（软骨细胞、成骨细胞、破骨细胞、骨细胞和成肌细胞）在单独引发 OA 的发展和进展中或通过与巨噬细胞/滑膜细胞的相互作用中的作用。相应地，我们总结了目前基于上述理论的针对 OA 的靶向治疗方法，例如，通过消除衰老的骨骼细胞和/或抑制驱动衰老的衰老相关分泌表型（SASP）。此外，还强调了现有的从衰老角度研究 OA 的动物模型，以填补基础研究和临床应用之间的空白。总的来说，在这篇综述中，我们系统地评估了细胞衰老在 OA 中的当前理解，这反过来可能为 OA 的分层治疗提供思路。
