Eosinophils-Induced Lumican Secretion by Synovial Fibroblasts Alleviates Cartilage Degradation via the TGF-β Pathway Mediated by Anxa1 Binding.

Abstract

The innate immune response is crucial in the progression of temporomandibular joint osteoarthritis (TMJOA). Yet, the roles of eosinophils in TMJOA remain unclear, underscoring the need for further investigation into their potential impact and mechanism. Addressing the clinical observation that eosinophil numbers in synovial fluid are higher in healthy individuals than in those with TMJOA, the vital regulation of this cell population in TMJOA by using an ovalbumin (OVA)-induced hyper-eosinophilia asthma rats is explored and a rat model of antibody-mediated eosinophil depletion in vivo, and co-culture system of synovial fibroblasts, chondrocytes, and eosinophils in vitro. The abnormal synovial proliferation, cartilage degradation, and subchondral bone erosion are effectively inhibited in OVA-induced asthmatic rats appearing in the local accumulation of eosinophils in the synovium. Conversely, the reduction in synovial eosinophils exacerbated TMJOA in rats treated with TRFK. Mechanistically, the protective effect of eosinophils against TMJOA is attributed to their promotion of Lumican secretion in the synovium, where Lumican binds to Annexin A1 in chondrocytes, inhibits transforming growth factor β2 Annexin A1 and Smad2/3 phosphorylation. These results illustrate OVA/IL-5-induced eosinophils' crucial role in TMJOA, identifying Lumican as a key anti-TMJOA target. Collectively, these findings revealed the signature and mechanism in eosinophils that stimulate TMJOA resolution.