LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis

作者全名："Du, Chengcheng; Cheng, Qiang; Zhao, Piao; Wang, Claire; Zhu, Zhenglin; Wu, Xiangdong; Gao, Shengqiang; Chen, Bowen; Zou, Jing; Huang, Wei; Liao, Junyi"

作者地址："[Du, Chengcheng; Cheng, Qiang; Zhu, Zhenglin; Gao, Shengqiang; Chen, Bowen; Zou, Jing; Huang, Wei; Liao, Junyi] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, Chongqing 400016, Peoples R China; [Du, Chengcheng; Cheng, Qiang; Zhao, Piao; Zhu, Zhenglin; Gao, Shengqiang; Chen, Bowen; Zou, Jing; Huang, Wei; Liao, Junyi] Chongqing Med Univ, Orthoped Lab, Chongqing 400016, Peoples R China; [Zhao, Piao] Univ Chicago, Dept Orthoped Surg & Rehabil Med, Mol Oncol Lab, Med Ctr, Chicago, IL 60637 USA; [Wang, Claire] Rice Univ, Dept Computat & Appl Math, Houston, TX 77005 USA; [Wu, Xiangdong] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Orthoped Surg, Beijing 100730, Peoples R China"

通信作者："Huang, W; Liao, JY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001017301800001

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：10

期号：3

开始页：1040

结束页：1054

文献类型：Article

关键词：Angiogenesis; BMP9; Bone tissue engineering; LncRNA H19; Mesenchymal stem cells

摘要："BMP9 mediated osteogenic differentiation mechanisms of MSCs were widely explored, however, mechanisms of BMP9-induced angiogenesis still need to be clarified. We previously characterized that Notch1 promoted BMP9-induced osteogenesis-angiogenesis coupling process in mesenchymal stem cells (MSCs). Here, we explored the underlying mech-anisms of lncRNA H19 (H19) mediated regulation of BMP9-induced angiogenesis through acti-vating Notch1 signaling. We demonstrated that basal expression level of H19 was high in MSCs, and silencing H19 attenuates BMP9-induced osteogenesis and angiogenesis of MSCs both in vitro and in vivo. Meanwhile, we identified that BMP9-induced production of CD31 thorn cells was indispensable for BMP9-induced bone formation, and silencing H19 dramatically blocked BMP9- induced production of CD31 thorn cells. In addition, we found that down-regulation of H19 inhibited BMP9 mediated blood vessel formation and followed subsequent bone formation in vivo. Mech-anistically, we clarified that H19 promoted p53 phosphorylation by direct interacting and phos-phorylating binding, and phosphorylated p53 potentiated Notch1 expression and activation of Notch1 targeting genes by binding on the promoter area of Notch1 gene. These findings sug-gested that H19 regulated BMP9-induced angiogenesis of MSCs by promoting the p53-Notch1 angiogenic signaling axis.& COPY; 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of China, PRC [82002312, 81972069]; Science and Technology Research Program of Chongqing Education Commission, PRC [KJQN202100431, KJZD-M202100401]; Candidate of Tip-Top Talent of the First Affiliated Hospital of Chongqing Medical University, PRC [BJRC2021-04]; Natural Science Foundation of Chongqing Science and Technology Commission, PRC [cstc2018jcyjAX0088]"

基金资助正文："The reported work was supported by the National Natural Science Foundation of China, PRC (No. #82002312 and #81972069). This project was also supported by Science and Technology Research Program of Chongqing Education Commission, PRC (No. #KJQN202100431 and #KJZD-M202100401), Candidate of Tip-Top Talent of the First Affiliated Hospital of Chongqing Medical University, PRC (No. BJRC2021-04) and Natural Science Foundation of Chongqing Science and Technology Commission, PRC (No. #cstc2018jcyjAX0088). Dr Liao is a postdoctoral fellow of & nbsp;Chongiqng Medical University. Funding sources were not involved in the study design, in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication."