This federal Project Grant award of $621,703.00 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) will support research at Cornell University to investigate the mechanisms for promoting a reparative rather than degenerative outcome from loading of fatigue-damaged tendons. The key objectives are to: 1) Determine how increases in glycosaminoglycans modulate the mechanical environment of cells in damaged tendons, leading to increased populations of alpha-smooth muscle actin (αSMA) positive cells and integrin α5; 2) Evaluate how the increase in αSMA positive cells decreases the area of severe matrix damage and mediates tissue repair; and 3) Assess how integrin α5 protects cells from apoptosis but also promotes a catabolic response in some cell types while enhancing functionality in others. The proposed research will employ in vivo models, pharmacological interventions, and single-cell RNA sequencing to elucidate these mechanisms, with the goal of informing diagnostics and therapeutics for managing tendon injuries.
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