MiR-601-induced BMSCs senescence accelerates steroid-induced osteonecrosis of the femoral head progression by targeting SIRT1

作者全名："Tang, Boyu; Chen, Yu; Zhao, Pei; Yan, Wenlong; Huang, Xiao; Jiang, Weiqian; Sun, Mingjie; Zhang, Hongrui; Xiang, Dulei; Chen, Tingmei; Lian, Chengjie; Zhang, Jian"

作者地址："[Tang, Boyu; Chen, Yu; Zhao, Pei; Yan, Wenlong; Huang, Xiao; Jiang, Weiqian; Sun, Mingjie; Zhang, Hongrui; Xiang, Dulei; Lian, Chengjie; Zhang, Jian] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400000, Peoples R China; [Tang, Boyu; Chen, Yu; Zhao, Pei; Yan, Wenlong; Huang, Xiao; Jiang, Weiqian; Sun, Mingjie; Zhang, Hongrui; Xiang, Dulei; Lian, Chengjie; Zhang, Jian] Chongqing Med Univ, Orthoped Lab, Chongqing, Peoples R China; [Chen, Tingmei] Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing, Peoples R China"

通信作者："Lian, CJ; Zhang, J (通讯作者)，Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400000, Peoples R China.; Lian, CJ; Zhang, J (通讯作者)，Chongqing Med Univ, Orthoped Lab, Chongqing, Peoples R China."

来源：CELLULAR AND MOLECULAR LIFE SCIENCES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001050715400003

JCR分区：Q1

影响因子：6.2

年份：2023

卷号：80

期号：9

开始页：　

结束页：　

文献类型：Article

关键词：Steroid-induced osteonecrosis of the femoral head; Bone marrow mesenchymal stem cells; Cell senescence; miR-601; SIRT1

摘要："BackgroundThe imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is not only the primary pathological feature but also a major contributor to the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH). Cellular senescence is one of the main causes of imbalanced BMSCs differentiation. The purpose of this study was to reveal whether cellular senescence could participate in the progression of SONFH and the related mechanisms.MethodsThe rat SONFH model was constructed, and rat BMSCs were extracted. Aging-related indicators were detected by SA-& beta;-Gal staining, qRT-PCR and Western Blot experiments. Using H2O2 to construct a senescent cell model, and overexpressing and knocking down miR-601 and SIRT1 in hBMSCs, the effect on BMSCs differentiation was explored by qRT-PCR, Western Blot experiment, oil red O staining (ORO), alizarin red staining (ARS), and luciferase reporter gene experiment. A rat SONFH model was established to test the effects of miR-601 and metformin in vivo.ResultsThe current study showed that glucocorticoids (GCs)-induced BMSCs senescence, which caused imbalanced osteogenesis and adipogenesis of BMSCs, was responsible for the SONFH progression. Further, elevated miR-601 caused by GCs was demonstrated to contribute to BMSCs senescence through targeting SIRT1. In addition, the anti-aging drug metformin was shown to be able to alleviate GCs-induced BMSCs senescence and SONFH progression.ConclusionsConsidering the role of BMSCs aging in the progression of SONFH, this provides a new idea for the prevention and treatment of SONFH."

基金机构："Natural Science Foundation of China [32271179, 82102610]; Chongqing Technology Innovation and Application Development Project [CQYC202010]; Natural Science Foundation of Chongqing Science and Technology Commission [cstc2020jcyj-msxmX0179]; Science Foundation for Top-notch Young Scholars of the First Affiliated Hospital of Chongqing Medical University [BJRC2021-02]; Science and Technology Research Project of Chongqing Sports Bureau [A202206, A202013, C202124]; Science and Technology Research Project of Chongqing Education Commission [KJQN202200404]"

基金资助正文："The study was supported by the Natural Science Foundation of China (No. 32271179, 82102610); Chongqing Technology Innovation and Application Development Project (CQYC202010); the Natural Science Foundation of Chongqing Science and Technology Commission (No. cstc2020jcyj-msxmX0179); the Science Foundation for Top-notch Young Scholars of the First Affiliated Hospital of Chongqing Medical University (No. BJRC2021-02); the Science and Technology Research Project of Chongqing Sports Bureau (No. A202206, A202013, C202124); and the Science and Technology Research Project of Chongqing Education Commission (No. KJQN202200404). All the funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript."