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.