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Targeting endothelial PDGFR-β facilitates angiogenesis-associated bone formation through the PAK1/NICD axis.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2024 Aug; Vol. 239 (8), pp. e31291. Date of Electronic Publication: 2024 May 09. - Publication Year :
- 2024
-
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.<br /> (© 2024 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
- Subjects :
- Animals
Humans
Female
Mice
Endothelial Cells metabolism
Mice, Inbred C57BL
Human Umbilical Vein Endothelial Cells metabolism
Angiogenesis
Receptor, Platelet-Derived Growth Factor beta metabolism
Receptor, Platelet-Derived Growth Factor beta genetics
p21-Activated Kinases metabolism
p21-Activated Kinases genetics
Osteogenesis
Signal Transduction
Neovascularization, Physiologic
Receptor, Notch1 metabolism
Receptor, Notch1 genetics
Osteoporosis metabolism
Osteoporosis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 239
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 38721633
- Full Text :
- https://doi.org/10.1002/jcp.31291