Abstract
Diabetes mellitus type 2 (DMT2) promotes Achilles tendon (AS) degeneration and exercise could modulate features of DMT2. Hence, this study investigated whether tenocytes of non DMT2 and DMT2 rats respond differently to normo- (NG) and hyperglycemic (HG) conditions in the presence of tumor necrosis factor (TNF)α or cyclic stretch. AS tenocytes, isolated from DMT2 (fa/fa) or non DMT2 (lean, fa/+) adult Zucker Diabetic Fatty (ZDF) rats, were treated with 10 ng/mL TNFα either under NG or HG conditions (1 g/L vs. 4.5 g/L glucose) and were exposed to cyclic stretch (14%, 0.3 Hz, 48 h). Tenocyte survival, metabolic activity, gene and/or protein expression of tendon extracellular matrix component collagen type 1, alpha smooth muscle actin (αSMA, Acta2), the stress defense enzyme heme oxygenase-1 (Hmox1) as well as suppressors of cytokine signaling (Socs)1 and Socs3 were analyzed. Tenocyte vitality remained high, but metabolic activity was slightly impaired by HG conditions irrespectively of cell origin. Collagen type 1 alpha protein and gene expression was suppressed by TNFα, but only in cells of non DMT2 animals in NG culture medium. Higher amounts of αSMA were visualized in tendons/tenocytes of diabetic rats or those exposed to TNFα. Cyclic stretch caused cell alignment in zero stretch direction. In addition, it led to a significant reduction of cell perimeters, particularly in cells of DMT2 donor rats under HG conditions. Hmox1, Socs1 and Socs3 were induced by HG, but only in tenocytes of diabetic rats (4 h). Stretch induced significantly Hmox1 transcriptional activity under NG conditions and Socs3 under HG conditions especially in tenocytes of DMT2 rats. The response of tenocytes to TNFα and cyclic stretch depends on glucose supply and origin suggesting their irreversible impairment by DMT2.