High glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway
Journal
Scientific Reports
Journal Volume
7
Pages
44199
Date Issued
2017
Author(s)
Abstract
Diabetes mellitus (DM) is associated with higher risk of tendinopathy, which reduces tolerance to exercise and functional activities and affects lifestyle and glycemic control. Expression of tendon-related genes and matrix metabolism in tenocytes are essential for maintaining physiological functions of tendon. However, the molecular mechanisms involved in diabetic tendinopathy remain unclear. We hypothesized that high glucose (HG) alters the characteristics of tenocyte. Using in vitro 2-week culture of tenocytes, we found that expression of tendon-related genes, including Egr1, Mkx, TGF-β1, Col1a2, and Bgn, was significantly decreased in HG culture and that higher glucose consumption occurred. Down-regulation of Egr1 by siRNA decreased Scx, Mkx, TGF-β1, Col1a1, Col1a2, and Bgn expression. Blocking AMPK activation with Compound C reduced the expression of Egr1, Scx, TGF-β1, Col1a1, Col1a2, and Bgn in the low glucose condition. In addition, histological examination of tendons from diabetic mice displayed larger interfibrillar space and uneven glycoprotein deposition. Thus, we concluded that high glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway and the expression of downstream tendon-related genes in tenocytes. The findings render a molecular basis of the mechanism of diabetic tendinopathy and may help develop preventive and therapeutic strategies for the pathology. ? The Author(s) 2017.
SDGs
Other Subjects
early growth response factor 1; Egr1 protein, rat; glucose; hydroxymethylglutaryl coenzyme A reductase kinase; achilles tendon; animal; down regulation; drug effect; metabolism; pathology; rat; signal transduction; Sprague Dawley rat; tendinitis; tenocyte; Achilles Tendon; AMP-Activated Protein Kinases; Animals; Down-Regulation; Early Growth Response Protein 1; Glucose; Rats; Rats, Sprague-Dawley; Signal Transduction; Tendinopathy; Tenocytes
Publisher
Nature Publishing Group
Type
journal article