TY - JOUR
T1 - Alleviation of osteoarthritis progression through far-infrared therapy targeting osteoclast cytoskeleton and MAPK/c-Fos/NFATc1 signaling inhibition
AU - Qin, Bo
AU - Lu, Heng ao
AU - Xu, Xiong fei
AU - Yang, Jiu jie
AU - Wang, Yu ping
AU - Zhang, Huan Tian
AU - Fu, Shi jie
AU - Qu, Yuan qing
AU - Wu, Wan yu
AU - Zheng, Wu yan
AU - Xu, Yu lin
AU - Sit, Cheok Lan
AU - Law, Betty Yuen Kwan
AU - Wang, Nick
AU - Xu, Yong
AU - Wong, Vincent Kam Wai
N1 - Publisher Copyright:
© 2026 The Authors
PY - 2026/6
Y1 - 2026/6
N2 - 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.
AB - 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.
KW - Cytoskeleton
KW - Far infrared radiation
KW - Osteoarthritis
KW - Osteoclast
KW - Subchondral bone remodeling
UR - https://www.scopus.com/pages/publications/105037876255
U2 - 10.1016/j.phrs.2026.108221
DO - 10.1016/j.phrs.2026.108221
M3 - Article
AN - SCOPUS:105037876255
SN - 1043-6618
VL - 228
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 108221
ER -