<i>Schistosoma japonicum</i> ‐Derived Peptide <scp>SJMHE1</scp> Attenuates Osteoarthritis by Promoting Synovial <scp>M2</scp> Macrophage Polarisation

Osteoarthritis (OA), a degenerative condition, severely impacts the quality of life in elderly individuals. Current clinical treatment options for OA remain limited. The polarisation of synovial macrophages plays a pivotal role in OA progression. SJMHE1, a peptide derived from Schistosoma japonicum (S. japonicum), has demonstrated the ability to inhibit inflammatory responses such as those seen in asthma and enteritis. Herein, SJMHE1 was administered via intra-articular injection to rats with anterior cruciate ligament transection (ACLT)-induced OA. Its effects on synovial inflammation, cartilage degradation and macrophage polarisation were assessed. Additionally, SJMHE1-stimulated macrophages were co-cultured with chondrocytes to examine chondrocyte degradation and apoptosis. The effect of the peptide on the expression of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) derived from patients with OA was also evaluated. SJMHE1 treatment delayed OA progression in elderly rats. It inhibited M1 macrophage polarisation, promoted M2 macrophage polarisation, reduced synovial inflammation and alleviated cartilage degradation. In the synovium, SJMHE1 downregulated proinflammatory cytokine IL-6 and upregulated the anti-inflammatory cytokine IL-10. In vitro, SJMHE1-treated macrophages preserved chondrogenic properties and inhibited chondrocyte apoptosis. Furthermore, SJMHE1 suppressed inflammatory cytokine production in PBMCs from patients with OA. The results suggest that SJMHE1 could represent a potential therapeutic approach for managing OA.