Targeting p21-Positive Senescent Chondrocytes via IL-6R/JAK2 Inhibition to Alleviate Osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is an age-related degenerative joint disease, prominently influenced by the pro-inflammatory cytokine interleukin-6 (IL-6). Although elevated IL-6 levels in joint fluid are well-documented, the uneven cartilage degeneration observed in knee OA patients suggests additional underlying mechanisms. This study investigates the role of interleukin-6 receptor (IL-6R) in mediating IL-6 signaling and its contribution to OA progression. Here, significantly elevated IL-6R expression is identified in degenerated cartilage of OA patients. Further, in vivo experiments reveal that intra-articular injection of recombinant IL-6R protein or activation of gp130 (Y757F mutation) accelerates OA progression. Conversely, knockout of IL-6R or JAK2, as well as treatment with a JAK inhibitor, al

SUBMITTER: Zhao X 

PROVIDER: S-EPMC11923994 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature