PPP3R1 Promotes MSCs Senescence by Inducing Plasma Membrane Depolarization and Increasing Ca2+ Influx

作者全名："Li, Molin; Gong, Weimin; Chen, Jie; Zhang, Yining; Ma, Yufei; Tu, Xiaolin"

作者地址："[Li, Molin; Gong, Weimin; Chen, Jie; Zhang, Yining; Ma, Yufei; Tu, Xiaolin] Chongqing Med Univ, Inst Life Sci, Lab Skeletal Dev & Regenerat, Chongqing 400016, Peoples R China"

通信作者："Ma, YF; Tu, XL (通讯作者)，Chongqing Med Univ, Inst Life Sci, Lab Skeletal Dev & Regenerat, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000947365300001

JCR分区：Q1

影响因子：4.9

年份：2023

卷号：24

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：BMSC; aging; Ca2+; membrane potential

摘要："Aging of mesenchymal stem cells(MSCs) has been widely reported to be strongly associated with aging-related diseases, including osteoporosis (OP). In particular, the beneficial functions of mesenchymal stem cells decline with age, limiting their therapeutic efficacy in age-related bone loss diseases. Therefore, how to improve mesenchymal stem cell aging to treat age-related bone loss is the current research focus. However, the underlying mechanism remains unclear. In this study, protein phosphatase 3, regulatory subunit B, alpha isoform, calcineurin B, type I (PPP3R1) was found to accelerate the senescence of mesenchymal stem cells, resulting in reduced osteogenic differentiation and enhanced adipogenic differentiation in vitro. Mechanistically, PPP3R1 induces changes in membrane potential to promote cellular senescence by polarizing to depolarizing, increasing Ca2+ influx and activating downstream NFAT/ATF3/p53 signaling. In conclusion, the results identify a novel pathway of mesenchymal stem cell aging that may lead to novel therapeutic approaches for age-related bone loss."

基金机构："National Natural Science Foundation of China [82072450, 82002310]; CQMU Program for Youth Innovation in Future Medicine [W0075]"

基金资助正文："This research was funded by the National Natural Science Foundation of China 82072450 (X.T.), 82002310 (Y.M.), and the CQMU Program for Youth Innovation in Future Medicine, W0075 (Y.M.)."