Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair.

ABSTRACT:

Objective

Human adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs.

Method

SUBMITTER: Shkhyan R 

PROVIDER: S-EPMC8444286 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature