Abstract
Type II Diabetes (T2DM) negatively alters baseline tendon function, including decreased range of motion and mechanical properties. The biological mechanisms that promote diabetic tendinopathy are unknown. To facilitate identification of therapeutic targets we developed a novel murine model of diabetic tendinopathy that results in progressive impairments in tendon extracellular matrix organization, gliding function and mechanical properties. Furthermore, restoration of normal metabolic function is insufficient to halt the pathological changes in tendon due to obesity/T2DM. Mechanistically, Insulin Receptor (IRβ) expression is increased in diabetic human tendon, while IRβ signaling is decreased in obese/T2DM murine tendons, suggesting altered IRβ signaling as a driver of diabetic tendinopathy. Conditional deletion of IRβ in tendon is not sufficient to induce diabetic tendinopathy, suggesting that obesity may be the predominant driver of this pathology. Collectively, these data define a murine model of diabetic tendinopathy, and demonstrate that tendon-specific, rather than systemic treatment approaches are needed.
