MCP-1 Exacerbates Diabetic Rotator Cuff Tear by Driving Synovial Inflammation via MAPK/ERK-Mediated Macrophage Polarization

Background Diabetic patients exhibit a high incidence and severe clinical manifestations of rotator cuff tear (RCT), yet the etiopathogenesis remains poorly defined. This study investigates the pathological characteristics and mechanisms underlying diabetic rotator cuff pathology. Methods and results We identified significantly elevated synovial inflammation and MCP-1 expression in affected patients. These findings were recapitulated in diabetic murine rotator cuff models, which demonstrated exacerbated synovitis ( IFN-γ, IL-1β, and TNF-α ), intense pain, functional impairment, and accelerated tendon degeneration. Critically, synovium-specific Ccl2 knockdown attenuated diabetes-associated degenerative progression. Mechanistically, MCP-1 primarily binds CCR2 receptors to amplify inflammatory mediator release. Subsequent MAPK/ERK pathway activation drives pro-inflammatory M1 macrophage polarization, thereby aggravating synovitis and precipitating the clinical triad of severe pain, functional disability, and tendon degeneration. Pharmacological inhibition of MCP-1 in vivo significantly reversed diabetes-induced synovial inflammation. Conclusions Our work elucidates the pathogenic cascade driving severe degeneration in diabetic rotator cuff disorders and nominates MCP-1 as a promising therapeutic target.