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

Yuanyuan Gao1, Wenshuang Sun2, Junrui Wang3

  • 1Nanjing 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.

Insights

Oxidative stress damages tendon stem cells (TSCs) in tendinopathy through ferroptosis. Targeting the cGAS-STING pathway may offer a new therapeutic strategy for this common sports injury.

Area of Science:

  • Orthopedics
  • Cell Biology
  • Biochemistry

Background:

  • Tendinopathy is a common orthopedic sports injury with limited effective treatments.
  • Oxidative stress is known to injure tendon stem cells (TSCs) during tendinopathy, but the underlying mechanisms remain unclear.

Purpose of the Study:

  • To investigate the mechanism of oxidative damage to TSCs in tendinopathy.
  • To explore the role of the cGAS-STING pathway and mitophagy in H2O2-induced TSC injury.
  • To evaluate cGAS as a potential therapeutic target for tendinopathy.

Main Methods:

  • Induction of oxidative damage in TSCs using hydrogen peroxide (H2O2).
  • Assessment of ferroptosis, mitophagy, and the cGAS-STING pathway activation.
  • Inhibition of mitophagy using Mdivi-1 and interference with cGAS function.
  • Evaluation of therapeutic effects in a rat model of tendinopathy.

Main Results:

  • H2O2 induces oxidative damage in TSCs via ferroptosis and increases mitophagy.
  • Inhibiting mitophagy with Mdivi-1 attenuates H2O2-induced ferroptosis.
  • H2O2 activates the cGAS-STING pathway, which regulates mitophagy.
  • Interfering with cGAS impairs mitophagy and ferroptosis, and alleviates tendon injury in rats.

Conclusions:

  • Oxidative stress induces TSC injury in tendinopathy through ferroptosis, modulated by mitophagy and the cGAS-STING pathway.
  • Targeting the cGAS-STING pathway offers a novel therapeutic strategy for tendinopathy treatment.

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