Hyperglycemia Reduces Proteoglycan Levels in Tendons

Abstract

Rationale: Diabetic tendinopathy is characterized by increased stiffness, thickness, and excess calcification of affected tendons. We investigated the hypothesis that proteoglycans (PGs), as key regulators of tendon structure and calcification, are altered in diabetic tendons.Methods: Adult porcine patellar tendons were incubated in iso-osmolar media with high or normal glucose levels for 2 weeks. The PG fraction was isolated and analyzed. Protein and mRNA levels of five PGs were measured. PG production was assessed in primary tenocyte monolayers by 35S-sulfate labeling in high and normal glucose conditions with and without exposure to advanced glycation end-products (AGEs). Levels of transforming growth factor β, which commonly mediates some effects of hyperglycemia, were also measured and the effects of free radical scavengers on 35S-sulfate incorporation were determined.Results: PG levels were significantly decreased in tendons exposed to high glucose media compared with tendons in iso-osmolar control media. Relative quantities of individual PGs were unchanged by exposure to hyperglycemia and mRNAs for PGs were variably affected. High glucose media decreased PG production by tenocytes as measured by 35S-sulfate labeling, whereas AGE-modified type I collagen and free radical scavengers had no effects. Hyperglycemic conditions increased levels of transforming growth factor β1 in an AGE-independent manner.Conclusions: Hyperglycemia produces a reduction in PG levels related to decreased synthesis or sulfation of glycosaminoglycans, which may contribute to the tendon pathology observed clinically in diabetes.