CDK8 mediated inflammatory microenvironment aggravates osteoarthritis progression

作者：Zhongnan Lin, Yining Xu, Hongyi Jiang, Wen Zeng, Yuhan Wang, Liang Zhu, Chihao Lin, Chao Lou, Hanting Shen, Ye Han, Yue Gu, Huachen Yu, Xiaoyun Pan, Lin Zheng · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.017 · 被引用次数：15 · 研究领域：Osteoarthritis Treatment and Mechanisms、Bone Metabolism and Diseases、Genomics and Chromatin Dynamics

• CDK8 exerts its role in the progression of OA by influencing the transcriptional regulation of SASP genes through NF-κB. • The mechanism by which CDK8 affects transcriptional regulation is through its cooperative recruitment with NF-κB to the promoters of SASP genes, followed by the promotion of Rpb1 CTD elongation phosphorylation in the gene-specific context induced by NF-κB. • The expression level of CDK8 can affect the nuclear translocation of p65. • Our study shows that based on ELISA detection of synovial fluid, serum, and cell culture supernatants, the secretion level of SASP may be positively correlated with the progression of OA, providing potential biomarkers for determining the severity of OA. • In the development of OA, CDK8 not only affects the degradation of chondrocytes themselves but also promotes the inflammatory joint microenvironment and osteoclast differentiation of macrophages by regulating the secretion of SASP from chondrocytes. Cyclin-Dependent Kinase 8 (CDK8), a CDK family member, regulates the development of inflammatory processes through transcriptional activation. The involvement of CDK8 in osteoarthritis (OA) progression is not yet understood. This study aims to investigate whether CDK8, through its transcriptional regulatory functions, collaborates with NF-κB in chondrocytes to regulate the transcription of senescence-associated secretory phenotype (SASP) genes, thereby exacerbating the inflammatory microenvironment in the progression of osteoar...