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

Hancheng Lin; Rongmin Lin; Jiahui Hou; Chencheng Zhu; Guanqiao Liu; Yihuang Lin; Jianwen Su; Mankai Yang; Bingsheng Yang; Yuan Ma; Caiyu Cheng; Mingye Deng; Bin Yu; Ting Xu; HangTian Wu; Zhuang Cui

doi:10.1002/jcp.31291

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

J Cell Physiol. 2024 May 9. doi: 10.1002/jcp.31291. Online ahead of print.

Authors

Hancheng Lin^{1

2}, Rongmin Lin^{1

2}, Jiahui Hou^{1

2}, Chencheng Zhu^{1

2}, Guanqiao Liu^{1

2}, Yihuang Lin^{1

2}, Jianwen Su^{1

2}, Mankai Yang^{1

2}, Bingsheng Yang^{1

2}, Yuan Ma^{1

2}, Caiyu Cheng^{1

2}, Mingye Deng^{1

2}, Bin Yu^{1

2}, Ting Xu³, HangTian Wu^{1

2}, Zhuang Cui^{1

2}

Affiliations

¹ Department of Orthopaedics, Division of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
² Division of Orthopaedics and Traumatology, Guangdong Provincial Key Laboratory of Bone and Cartilage Regeneration Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
³ Department of Sleep Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

PMID: 38721633
DOI: 10.1002/jcp.31291

Abstract

The 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.

Keywords: H‐type vessels; NICD; PAK1; PDGFR‐β; osteoporosis.

Abstract

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