Hyperoxia promotes osteogenic differentiation of diabetic tendon stem/progenitor cells via ROS/HIF-1a signaling axis

Diabetic calcified tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) play important roles in the pathogenesis of diabetic calcified tendinopathy. However, the molecular mechanisms remain unclear. In this study, we first found that blood vessels and hemoglobin increased significantly in the Achilles tendons of diabetic rats, indicating the existence of a hyperoxic environment in diabetic tendons. We found that hyperoxia promoted the osteogenic differentiation of TSPCs in vitro. Simultaneously, hyperoxia caused the change of reactive oxygen species (ROS)/hypoxia-inducible factor-1a (HIF-1a) signaling axis in TSPCs. In addition, N-acetyl-L-cysteine (NAC) intervention showed that blocking the ROS/HIF-1a signaling axis significantly inhibited the enhanced osteogenic differentiation ability of TSPCs induced by hyperoxia. In vivo, animal experiments indicated that NAC effectively inhibited hydrogen peroxide-induced calcification of Achilles tendons. In a word, hyperoxia promotes osteogenic differentiation of diabetic tendon stem/progenitor cells via ROS/HIF-1a signaling axis and provides a new theoretical basis for preventing and treating diabetic calcified tendinopathy.