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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.<\/jats:p>","DOI":"10.1038\/s42003-024-05915-1","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T12:20:15Z","timestamp":1710332415000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Endothelial SMAD1\/5 signaling couples angiogenesis to osteogenesis in juvenile bone"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-9476","authenticated-orcid":false,"given":"Annemarie","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Benn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique","family":"Wolter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Balcaen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-8324","authenticated-orcid":false,"given":"Greet","family":"Kerckhofs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1721","authenticated-orcid":false,"given":"An","family":"Zwijsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-3025","authenticated-orcid":false,"given":"Joel D.","family":"Boerckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"5915_CR1","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/9467","volume":"5","author":"H-P Gerber","year":"1999","unstructured":"Gerber, H.-P. et al. 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