Alleviation of osteoarthritis progression through far-infrared therapy targeting osteoclast cytoskeleton and MAPK/c-Fos/NFATc1 signaling inhibition.

This study investigated the anti-osteoclastic and chondroprotective effects of far-infrared (FIR) therapy in osteoarthritis (OA), focusing on its ability to modulate pathological osteoclast (OC) activation and subchondral bone remodeling. A monosodium iodoacetate (MIA)-induced OA rat model was used, and FIR's therapeutic potential was evaluated through longitudinal assessment of nociception (von Frey test), cartilage integrity (histomorphometry: H&E, TRAP, and safranin O/fast green staining), and subchondral microstructure (micro-CT). Complementary in vitro analyses of RANKL-stimulated osteoclastogenesis were performed, including transcriptomic profiling, cytoskeletal visualization, and proteomic validation. FIR intervention (30/60 min daily) significantly attenuated OA progression, demonstrating: (1) In vivo assessments demonstrated FIR produced time-dependent pain alleviation, with gradual relief observed over the course of treatment (P < 0.05). Early and mid-term (days 7/14) improvements were more pronounced, particularly in bone mineral density, cartilage integrity, and subchondral bone osteoclastogenesis suppression (P < 0.01). These effects diminished during the late intervention stage (days 28; P < 0.05). (2) Cellular studies showed FIR inhibited RANKL-mediated OC differentiation, as evidenced by reduced TRAP activity and downregulation of OC-specific markers (P < 0.05). (3) Transcriptomic analysis identified actin cytoskeleton reorganization and OC differentiation pathways as primary targets of FIR intervention. This finding was supported by disrupting F-actin ring formation and modulating key regulatory proteins via MAPK/c-Fos/NFATc1 signaling (P < 0.05). Our findings establish FIR therapy as an effective physical pharmacology strategy for OA management. It simultaneously addresses nociception, cartilage degeneration, and pathological bone remodeling through selective targeting of OC cytoskelet.