2. Academic Validation
  3. LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis

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

  • Genes Dis. 2022 May 10;10(3):1040-1054. doi: 10.1016/j.gendis.2022.04.013.
Chengcheng Du 1 2,  Qiang Cheng 1 2,  Piao Zhao 2 3,  Claire Wang 4,  Zhenglin Zhu 1 2,  Xiangdong Wu 5,  Shengqiang Gao 1 2,  Bowen Chen 1 2,  Jing Zou 1 2,  Wei Huang 1 2,  Junyi Liao 1 2
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
  • 2 Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China.
  • 3 Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
  • 4 Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA.
  • 5 Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
PMID: 37396541 DOI: 10.1016/j.gendis.2022.04.013
Abstract

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 mechanisms of lncRNA H19 (H19) mediated regulation of BMP9-induced angiogenesis through activating 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+ cells was indispensable for BMP9-induced bone formation, and silencing H19 dramatically blocked BMP9-induced production of CD31+ cells. In addition, we found that down-regulation of H19 inhibited BMP9 mediated blood vessel formation and followed subsequent bone formation in vivo. Mechanistically, we clarified that H19 promoted p53 phosphorylation by direct interacting and phosphorylating binding, and phosphorylated p53 potentiated Notch1 expression and activation of Notch1 targeting genes by binding on the promoter area of Notch1 gene. These findings suggested that H19 regulated BMP9-induced angiogenesis of MSCs by promoting the p53-Notch1 angiogenic signaling axis.

Keywords

Angiogenesis; BMP9; Bone tissue engineering; LncRNA H19; Mesenchymal stem cells.

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