Enhancing osteogenic differentiation of diabetic tendon stem/progenitor cells through hyperoxia: Unveiling ROS/HIF-1α signalling axis

IF 5.3
Ming Zhang, Guan-Chun Dai, Yuan-Wei Zhang, Pan-Pan Lu, Hao Wang, Ying-Juan Li, Yun-Feng Rui
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引用次数: 0

Abstract

Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers. In hyperoxic environment, TSPCs showed enhanced osteogenic differentiation and increased levels of reactive oxygen species (ROS). Additionally, hypoxia-inducible factor-1a (HIF-1a), a protein involved in regulating cellular responses to hyperoxia, was decreased in TSPCs by the ubiquitin-proteasome system. By intervening with antioxidant N-acetyl-L-cysteine (NAC) and overexpressing HIF-1a, we discovered that blocking the ROS/HIF-1a signalling axis significantly inhibited the osteogenic differentiation ability of TSPCs. Animal experiments further confirmed that hyperoxic environment could cause calcification in the Achilles tendon tissue of rats, while NAC intervention prevented calcification. These findings demonstrate that hyperoxia in diabetic tendons promotes osteogenic differentiation of TSPCs through the ROS/HIF-1a signalling axis. This study provides a new theoretical basis and research target for preventing and treating diabetic calcified tendinopathy.

Abstract Image

通过高氧增强糖尿病肌腱干/祖细胞的成骨分化:揭示 ROS/HIF-1α 信号轴
糖尿病钙化性肌腱病是导致糖尿病患者慢性疼痛、活动受限和肌腱断裂的主要原因。肌腱干/祖细胞(TSPCs)与糖尿病钙化性肌腱病的发生有关,但其分子机制仍不清楚。本研究发现,糖尿病肌腱具有高氧环境,其特点是氧输送通道和载体增加。在高氧环境中,TSPCs 的成骨分化增强,活性氧(ROS)水平升高。此外,低氧诱导因子-1a(HIF-1a)是一种参与调节细胞对高氧反应的蛋白质,它在 TSPCs 中通过泛素蛋白酶体系统减少。通过使用抗氧化剂N-乙酰-L-半胱氨酸(NAC)和过表达HIF-1a,我们发现阻断ROS/HIF-1a信号轴能显著抑制TSPCs的成骨分化能力。动物实验进一步证实,高氧环境可导致大鼠跟腱组织钙化,而 NAC 的干预可防止钙化。这些研究结果表明,糖尿病肌腱中的高氧环境可通过 ROS/HIF-1a 信号轴促进 TSPCs 的成骨分化。这项研究为预防和治疗糖尿病钙化性肌腱病提供了新的理论基础和研究目标。
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来源期刊
CiteScore
11.50
自引率
0.00%
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0
期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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