Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis

Abstract

BCP crystals and IL-6 form a positive feedback loop leading to OA. Targeting calcium-containing crystal formation and/or IL-6 are promising therapeutic strategies in OA.

Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis

“…A similar difference was previously observed in the effects of IL-6 blockade upstream or downstream of its interaction with its gp130 receptor,18 so Stat3 may be activated independent of IL-6 by other gp130 cytokines. Notably, several studies have pointed to the role of oncostatin M (OSM) in synovial inflammation or osteophyte-like bone proliferation in mouse models 31 32.…”

“…More recently, a positive feedback loop was identified between calcium-containing crystals and IL-6 leading to cartilage destruction 18. Despite these data, the mechanisms by which IL-6 elicits its effects in cartilage remain poorly known 19…”

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

“…OSM promotes matrix loss and disease progression 12 13. IL-6 suppresses chondrocyte proliferation,14 promotes mineralisation in AC,15 downregulates matrix proteins16 and increases expression of proteases 17 18. Moreover, blockade of IL-6 in mouse models of OA is chondroprotective 17 18.…”

The Role of ANK in Calcium Pyrophosphate Deposition Disease

“…Additional support for a role for inflammatory mediators in regulating ANK levels was recently supplied by Nasi et al They showed that IL-6, another important cytokine in crystal-induced arthritis, upregulated ANK, Annexin 5, and Pit-1 gene expression in murine cartilage explants [31]. …”