Platelet-Derived Growth Factor Receptor α positive Cells are Essential for Angiogenesis Coupled with Osteogenesis through Hypoxia Inducible Factor 1α Signaling

Backgroud: Bone remodeling is a lifelong process depending on two dynamic and balanced activities, bone resorption and formation. It was hypothesized that a subset of the smallest vessels is essential to promote bone formation. Questions: What are the cellular and molecular mechanisms that are involved in osteogenic vessel formation during bone remodeling༟ Results: We showed that bone marrow progenitor cells (BMPC) gave rise to endothelial cells for vessel formation during bone remodeling. We further found BMPCs were the targets for hypoxia inducible factor 1α (HIF1α) in vessel formation. Parathyroid hormone (PTH) is the only FDA-approved anabolic agent for osteoporosis. We found that PTH stimulated BMPCs commitment to endothelial cells for vessel formation and bone progenitors for bone formation. Inducible knockout of HIF1α from BMPCs abolished the effect of PTH in mouse models. Conclusion: BMPCs are essential for angiogenesis coupled with osteogenesis via HIF1α pathway. Clinical Relevance: HIF1α is a potential therapeutic target for osteoporosis.