Affiliation:
1. Department of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 China
2. Center for Biotherapy The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 China
Abstract
AbstractRegular 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.
Funder
Natural Science Foundation of Guangdong Province
National Natural Science Foundation of China
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)