Targeting endothelial PDGFR‐β facilitates angiogenesis‐associated bone formation through the PAK1/NICD axis

AbstractThe intricate orchestration of osteoporosis (OP) pathogenesis remains elusive. Mounting evidence suggests that angiogenesis‐driven osteogenesis serves as a crucial foundation for maintaining bone homeostasis. This study aimed to explore the potential of the endothelial platelet‐derived growth factor receptor‐β (PDGFR‐β) in mitigating bone loss through its facilitation of H‐type vessel formation. Our findings demonstrate that the expression level of endothelial PDGFR‐β is reduced in samples obtained from individuals suffering from OP, as well as in ovariectomy mice. Depletion of PDGFR‐β in endothelial cells ameliorates angiogenesis‐mediated bone formation in mice. The regulatory influence of endothelial PDGFR‐β on H‐type vessels is mediated through the PDGFRβ‐P21‐activated kinase 1‐Notch1 intracellular domain signaling cascade. In particular, the endothelium‐specific enhancement of PDGFR‐β facilitates H‐type vessels and their associated bone formation in OP. Hence, the strategic targeting of endothelial PDGFR‐β emerges as a promising therapeutic approach for the management of OP in the near future.