{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T18:51:29Z","timestamp":1768503089446,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,7]]},"group-title":"Developmental Biology","reference-count":47,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone development 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 cancellous and cortical bone formation. SMAD1\/5 depletion induced excessive sprouting, disrupting the columnar structure of the metaphyseal vessels and impaired anastomotic loop morphogenesis 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, featuring elevated endomucin expression, ectopic tip cell formation, and hyperpermeability. Together, endothelial SMAD1\/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics during bone growth.<\/jats:p>","DOI":"10.1101\/2023.01.07.522994","type":"posted-content","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T23:40:10Z","timestamp":1673134810000},"source":"Crossref","is-referenced-by-count":0,"title":["Endothelial SMAD1\/5 signaling couples angiogenesis to osteogenesis during long bone growth"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-9476","authenticated-orcid":false,"given":"Annemarie","family":"Lang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6559-0270","authenticated-orcid":false,"given":"Andreas","family":"Benn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-9355","authenticated-orcid":false,"given":"Angelique","family":"Wolter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5108-525X","authenticated-orcid":false,"given":"Tim","family":"Balcaen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5487-4294","authenticated-orcid":false,"given":"Joseph","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-8324","authenticated-orcid":false,"given":"Greet","family":"Kerckhofs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1721","authenticated-orcid":false,"given":"An","family":"Zwijsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-3025","authenticated-orcid":false,"given":"Joel D.","family":"Boerckel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023010907151366000_2023.01.07.522994v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90182-1"},{"key":"2023010907151366000_2023.01.07.522994v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1350705"},{"key":"2023010907151366000_2023.01.07.522994v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201241"},{"key":"2023010907151366000_2023.01.07.522994v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature13145"},{"key":"2023010907151366000_2023.01.07.522994v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1080320212"},{"key":"2023010907151366000_2023.01.07.522994v1.6","doi-asserted-by":"publisher","DOI":"10.1177\/00220345710500060601"},{"key":"2023010907151366000_2023.01.07.522994v1.7","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-200206000-00033"},{"key":"2023010907151366000_2023.01.07.522994v1.8","doi-asserted-by":"publisher","DOI":"10.1210\/en.143.4.1545"},{"key":"2023010907151366000_2023.01.07.522994v1.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-206433"},{"key":"2023010907151366000_2023.01.07.522994v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.02.017"},{"key":"2023010907151366000_2023.01.07.522994v1.11","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.118596"},{"key":"2023010907151366000_2023.01.07.522994v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.23010"},{"key":"2023010907151366000_2023.01.07.522994v1.13","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/j.biomaterials.2011.03.063","article-title":"Effects of protein dose and delivery system on BMP-mediated bone regeneration","volume":"32","year":"2011","journal-title":"Biomaterials"},{"key":"2023010907151366000_2023.01.07.522994v1.14","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2015.0357"},{"key":"2023010907151366000_2023.01.07.522994v1.15","doi-asserted-by":"crossref","unstructured":"E. 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