HIF1α Promotes BMP9-Mediated Osteoblastic Differentiation and Vascularization by Interacting with CBFA1

Figure 7

Proposed regulatory loop involving BMP9, HIF1α, and Runx2 in iMEFs. Runx2 and osteogenic marker factors are upregulated by BMP9 through BMP/Smad1/5/8 signaling to promote osteogenesis. A hypoxic environment leads to elevated HIF1α levels, which directly regulate the transcriptional function of Runx2 in the nucleus. Runx2 is an important target of HIF1α in iMEFs that regulates osteogenic differentiation in vitro and in vivo. Another possible important branch of the regulatory loop between HIF1α and osteogenesis is that HIF1α is a vital factor that plays a positive role in vascularization by regulating the expression of vasoformation-related regulators, including VEGF, CD31, vWF, and ANGPT1. Our initial results support the notion that the transcript activity of Runx2 is regulated by and coupled to HIF1α, which is enhanced by BMP9. This loop not only strengthens the osteogenic differentiation of iMEFs and angiogenesis mediated by HIF1α but also enhances extracellular matrix deposition and mineralization, which boosts efficient bone regeneration.