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Mechanistic study on stress-modulated regulation of knee osteoarthritis via shaking manipulation-induced synovial cell inflammatory signaling pathways
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DOI   10.11656/j.issn.1672-1519.2026.03.12
Key Words   shaking manipulation;KOA;synovitis;FLSs;signaling pathway;stress
Author NameAffiliationE-mail
WANG Yizhou Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China  
LONG Hailun Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China  
XING Anze Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China  
ZHAO Qiang Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China ywy0707@sina.com 
Abstract
    [Objective] This study aimed to investigate the mechanism by which shaking manipulation alleviates synovial inflammation in knee osteoarthritis(KOA) by regulating the αVβ3/FAK/ERK/C-Jun signaling pathway. [Methods] A total of 100 male New Zealand white rabbits were randomly divided into five groups(Normal,Sham,Model,Shaking,and Celecoxib;n=20 per group). The KOA model was induced by intra-articular injection of papain. The Shaking group received shaking manipulation treatment at a frequency of 0.5 Hz for 5 min once daily,and the Celecoxib group received intragastric administration of celecoxib solution,7 days per cycle for 3 cycles. Transmission electron microscopy was used to observe ultrastructural changes of synovial cells. Protein expression of αVβ3,FAK,ERK,and C-Jun was detected by Western blot,and mRNA expression was analyzed by RT-qPCR. Primary fibroblast-like synoviocytes(FLSs) were isolated using the tissue explant method. Levels of MMP-1 and MMP-13 in the culture supernatant were determined by radioimmunoassay,and F-actin cytoskeletal remodeling was observed by fluorescence staining. [Results] Shaking manipulation significantly improved synovial cell ultrastructure,downregulated the protein expression of αVβ3,FAK,ERK,and C-Jun(P<0.01),and reduced their mRNA levels(P<0.05). The secretion of MMP-1 and MMP-13 was significantly decreased(P<0.01). F-actin cytoskeletal remodeling was negatively correlated with inflammatory mediator secretion(P<0.05). [Conclusion] Shaking manipulation improves KOA synovitis by regulating the αVβ3/FAK/ERK/C-Jun signaling pathway,inducing cytoskeletal remodeling in synovial cells,and suppressing MMP secretion. This study provides molecular-level evidence for the efficacy of manipulation therapy in KOA and highlights the role of mechanical stress in synovial inflammation regulation.

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