LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of b-catenin BMSCs

作者全名："Jiang, Weiqian; Chen, Yu; Sun, Mingjie; Huang, Xiao; Zhang, Hongrui; Fu, Zheng; Wang, Jingjiang; Zhang, Shichun; Lian, Chengjie; Tang, Boyu; Xiang, Dulei; Wang, Yange; Zhang, Yulu; Jian, Changchun; Yang, Chaohua; Zhang, Jun; Zhang, Dian; Chen, Tingmei; Zhang, Jian"

作者地址："[Jiang, Weiqian; Chen, Yu; Sun, Mingjie; Huang, Xiao; Zhang, Hongrui; Lian, Chengjie; Tang, Boyu; Xiang, Dulei; Jian, Changchun; Yang, Chaohua; Zhang, Jun; Zhang, Jian] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing, Peoples R China; [Fu, Zheng] Binzhou Peoples Hosp, Dept Orthoped, Binzhou, Shandong, Peoples R China; [Wang, Jingjiang; Zhang, Shichun] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Wang, Yange; Zhang, Yulu; Zhang, Dian; Chen, Tingmei] Chongqing Med Univ, Coll Lab Med, Minist Educ, Key Lab Clin Lab Diagnost, Chongqing, Peoples R China"

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

来源：CELL REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001094892800001

JCR分区：Q1

影响因子：7.5

年份：2023

卷号：42

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid -induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of b-catenin. Ultimately, the nuclear localization of b-catenin decreases, and the differentiation balance of BMSCs tilts to-ward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target."

基金机构："National Natural Science Foundation of China [32271179, 81071490]; Chongqing Technology Innovation and Application Development Special Project [CQYC202010]; General Project of Chongqing Technology Innovation and Application Development Special Project [cstc2019jscx-msxmx0245]; Key project of Chongqing Municipal Health and Family Planning Commission [2017ZDXM006]"

基金资助正文："This work was supported by National Natural Science Foundation of China (32271179 and 81071490) , the Chongqing Technology Innovation and Application Development Special Project (CQYC202010) , the General Project of Chongqing Technology Innovation and Application Development Special Proj- ect (cstc2019jscx-msxmx0245) , and the Key project of Chongqing Municipal Health and Family Planning Commission (2017ZDXM006) ."