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TNF-α-Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy-Related Protein VCP.

Zepeng SuJinteng LiJiajie LinZhikun LiYunshu CheZhaoqiang ZhangGuan ZhengGuiwen YeWenhui YuYipeng ZengPeitao XuXiaojun XuZhongyu XieYanfeng WuHuiyong Shen
Published in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF-α is previously reported to regulate BMMSC functions, including multilineage differentiation and immunoregulation. The present study demonstrates that TNF-α impedes quiescence and promotes the activation of BMMSC in vitro and in vivo. Mechanistically, the TNF-α-induced expression of KAT2A promotes the succinylation of VCP at K658, which inhibits the interaction between VCP and MFN1 and thus inhibits mitophagy. Furthermore, activated BMMSC exhibits stronger fracture repair and immunoregulation functions in vivo. This study contributes to a better understanding of the mechanisms of BMMSC quiescence and activation and to improving the effectiveness of BMMSC in clinical applications.
Keyphrases
  • rheumatoid arthritis
  • stem cells
  • high glucose
  • diabetic rats
  • randomized controlled trial
  • poor prognosis
  • oxidative stress
  • primary care
  • endothelial cells
  • mesenchymal stem cells
  • binding protein
  • hip fracture