2. Academic Validation
  3. Oxidative stress induces ferroptosis in tendon stem cells by regulating mitophagy through cGAS-STING pathway

Oxidative stress induces ferroptosis in tendon stem cells by regulating mitophagy through cGAS-STING pathway

  • Int Immunopharmacol. 2024 Sep 10:138:112652. doi: 10.1016/j.intimp.2024.112652.
Yuanyuan Gao 1,  Wenshuang Sun 2,  Junrui Wang 3,  Danli Zhao 4,  Haoyuan Tian 3,  Yangling Qiu 3,  Shufan Ji 3,  Shuqi Wang 3,  Qiuyu Fu 3,  Feng Zhang 3,  Zili Zhang 3,  Feixia Wang 3,  Jiangjuan Shao 5,  Shizhong Zheng 6,  Jia Meng 7
Affiliations

Affiliations

  • 1 Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China.
  • 3 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 4 NanTong Health College of Jiangsu Province, Nantong 226000, China.
  • 5 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: jjshao@njucm.edu.cn.
  • 6 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: nytws@njucm.edu.cn.
  • 7 Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. Electronic address: michaelmengjia@163.com.
PMID: 38986301 DOI: 10.1016/j.intimp.2024.112652
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.

Keywords

Ferroptosis; Mitophagy; Oxidative stress; Tendinopathy; Tendon stem cell; cGAS-STING.

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