Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone
(2024) Communications biology — Vol. 7, n° 1, p. 315 [1-13] (2024)
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- Authors
Lang, Annemarie 
Boerckel, Joel D.
- Abstract
- (en) Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone formation in part by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered trabecular and cortical bone formation. SMAD1/5 depletion induced excessive sprouting and disrupting the morphology of the metaphyseal vessels, with impaired anastomotic loop formation at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long-term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops and elevated vascular permeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics in juvenile mouse bone.
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Citations
Lang, A., Benn, A., Collins, J. M., Wolter, A., Balcaen, T., Kerckhofs, G., Zwijsen, A., & Boerckel, J. D. (2024). Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone. Communications biology, 7(1), 315 [1-13]. https://doi.org/10.1038/s42003-024-05915-1 (Original work published 2024)