Abstract
Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.
Highlights
The dramatic increase in type II diabetes mellitus (T2DM) as part of the obesity epidemic [1], is one of the most critical health challenges facing the U.S.; in 2012 more than 29 million people, or nearly 10% of the US population were diabetic, resulting in a health care burden of $254 billion [2]
high fat diet (HFD) resulted in increased body weight and impaired glucose tolerance Body weights of mice in the HFD and low fat diet (LFD) groups were compared at the time of surgery (16 weeks of age, 12-weeks post-diet initiation) and the time of sacrifice
Fasting blood glucose (BG) was measured in both groups prior to surgery to confirm metabolic dysfunction and T2DM in HFD mice
Summary
The dramatic increase in type II diabetes mellitus (T2DM) as part of the obesity epidemic [1], is one of the most critical health challenges facing the U.S.; in 2012 more than 29 million people, or nearly 10% of the US population were diabetic, resulting in a health care burden of $254 billion [2]. T2DM results in systemic inflammation and is characterized by metabolic dysfunction including elevated plasma glucose levels (hyperglycemia). Among a plethora of systemic complications and co-morbidities arising from T2DM, the impact on the musculoskeletal system is emerging as an important disease manifestation. Rochester School of Medicine Office for Medical Education Year-out Research Fellowship. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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