Abstract：
Tendinopathy is one of the most prevalent sports injury diseases in orthopedics. However, there is no effective treatment or medicine. Recently, the discovery of tendon stem cells (TSCs) provides a new perspective to find new therapeutic methods for Tendinopathy. Studies have shown that oxidative stress will inevitably cause TSCs injury during tendinopathy, but the mechanism has not been fully elucidated. Here, we report the oxidative damage of TSCs induced by H2O2 via ferroptosis, as well, treatment with H2O2 raised the proportion of mitochondria engulfed by autophagosomes in TSCs. The suppression of mitophagy by Mdivi-1 significantly attenuates the H2O2-induced ferroptosis in TSCs. Mechanically, H2O2 actives the cGAS-STING pathway, which can regulate the level of mitophagy. Interfering with cGAS could impair mitophagy and the classical ferroptotic events. In the rat model of tendinopathy, interference of cGAS could relieve tendon injury by inhibiting ferroptosis. Overall, these results provided novel implications to reveal the molecular mechanism of tendinopathy, by which pointed to cGAS as a potential therapeutic target for the treatment of tendinopathy.
摘要：
肌腱病是骨科最常见的运动损伤性疾病之一。然而,没有有效的治疗或药物。最近,肌腱干细胞(TSCs)的发现为寻找治疗肌腱病的新方法提供了新的视角。研究表明,在肌腱病的发生过程中,氧化应激不可避免地会引起TSCs损伤,但机制尚未完全阐明。这里,我们报道了H2O2通过铁凋亡诱导的TSCs的氧化损伤，还有,H2O2处理提高了TSCs中自噬体吞噬的线粒体比例。Mdivi-1对线粒体自噬的抑制显着减弱了H2O2诱导的TSC铁凋亡。机械上,H2O2激活cGAS-STING途径，可以调节线粒体自噬的水平。干扰cGAS可能会损害线粒体自噬和经典的铁细胞事件。在肌腱病的大鼠模型中，cGAS的干预可以通过抑制铁性凋亡来减轻肌腱损伤。总的来说,这些结果为揭示肌腱病的分子机制提供了新的启示，其中指出cGAS是治疗肌腱病的潜在治疗靶点。
