Obesity/Type II Diabetes Promotes Function-limiting Changes in Murine Tendons that are not reversed by Restoring Normal Metabolic Function
Year: 2018
Type: article
Abstract: Type II Diabetes (T2DM) negatively alters baseline tendon function, including decreased range of motion and mechanical properties; however, the biological mechanisms that promote diabetic tendinopathy are unknown. To facilitate identification of therapeutic targets we developed a novel murine model of diabetic tendinopathy. Mice fed a High Fat Diet (HFD) developed diet induced obesity and T2DM and demonstrated progressive impairments in tendon gliding function and mechanical properties, relative to mice fed a Low Fat Diet (LFD). We then determined if restoration of normal metabolic function, by switching mice from HFD to LFD, was sufficient to halt the pathological changes in tendon due to obesity/T2DM. However, switching from a HFD to LFD resulted in greater impairments in tendon gliding function than mice maintained on a HFD. Mechanistically, IRβ signaling is decreased in obese/T2DM murine tendons, suggesting altered IRβ signaling as a driver of diabetic tendinopathy. However, knock-down of IRβ expression in S100a4-lineage cells (IRcKO S100a4 ) was not sufficient to induce diabetic tendinopathy as no impairments in tendon gliding function or mechanical properties were observed in IRcKO S100a4 , relative to WT. Collectively, these data define a murine model of diabetic tendinopathy, and demonstrate that restoring normal metabolism does not slow the progression of diabetic tendinopathy.
Source: Scientific Reports
Institutions: University of Rochester Medicine, University of Rochester
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G115179895, G1361315356, G1954440393, G2334450341, Engineering scarless repair of flexor tendon injuries, Modulation of Insertional Achilles Tendinopathy by Multiaxial Mechanical Strains, The University of Rochester Core Center for Musculoskeletal Biology and Medicine, G3301857500, Defining the relationship between attenuated insulin receptor signaling and fibrosis in diabetic tendinopathy, G3767295147, s100a4 Signaling in Fibrotic Diabetic Tendon Healing, Training in Orthopaedic Research, G9000035057, G9000103447, G9000294827
OpenAlex ID: W2808080300