Fermented mycelial extract from Auricularia heimuer and Sparassis crispa mitigates cartilage degeneration and inflammation in monosodium iodoacetate-induced osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, and chronic inflammation. This study investigated the anti-osteoarthritic effects of PS-ATJ301, a fermented mushroom mycelium prepared from Auricularia heimuer and Sparassis crispa . Metabolite profiling using UPLC-ESI-Q-TOF-MS demonstrated that fermentation enhanced steroidal saponin-associated metabolites in PS-ATJ301. OA was induced in SD rats using monosodium iodoacetate (MIA), followed by oral administration of PS-ATJ301 (100, 200, and 400 mg/kg/day) for 4 weeks. PS-ATJ301 improved weight-bearing capacity, preserved joint structural integrity, attenuated subchondral bone damage, and reduced cartilage erosion, proteoglycan depletion, and synovial tissue damage. PS-ATJ301 also suppressed inflammatory mediators (iNOS, COX-2, IL-1β, TNF-α, IL-6, NO, PGE2, and CRP), MMPs, COMP, and NF-κB signaling-related proteins, while restoring aggrecan and collagen II levels. In LPS-stimulated RAW264.7 macrophages, PS-ATJ301 inhibited TLR4/MyD88/NF-κB/NLRP3 signaling, reduced inflammatory cytokine and MMP expression, and promoted M2 macrophage polarization, suggesting its therapeutic potential against OA.