{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T04:23:35Z","timestamp":1793247815130,"version":"4.5.0"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAMS","award":["AR055607"],"award-info":[{"award-number":["AR055607"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,24]]},"abstract":"<jats:p>\n                    We present a transcriptomic analysis that provides a better understanding of regulatory mechanisms within the healthy and injured periosteum. The focus of this work is on characterizing early events controlling bone healing during formation of periosteal callus on day 3 after fracture. Building on our previous findings showing that induced Notch1 signaling in osteoprogenitors leads to better healing, we compared samples in which the Notch 1 intracellular domain is overexpressed by periosteal stem\/progenitor cells, with control intact and fractured periosteum. Molecular mechanisms and changes in skeletal stem\/progenitor cells (SSPCs) and other cell populations within the callus, including hematopoietic lineages, were determined. Notably, Notch ligands were differentially expressed in endothelial and mesenchymal populations, with\n                    <jats:italic>Dll4<\/jats:italic>\n                    restricted to endothelial cells, whereas\n                    <jats:italic>Jag1<\/jats:italic>\n                    was expressed by mesenchymal populations. Targeted deletion of\n                    <jats:italic>Dll4<\/jats:italic>\n                    in endothelial cells using Cdh5CreER resulted in negative effects on early fracture healing, while deletion in SSPCs using \u03b1-smooth muscle actin\u2013CreER did not impact bone healing. Translating these observations into a clinically relevant model of bone healing revealed the beneficial effects of delivering Notch ligands alongside the osteogenic inducer, BMP2. These findings provide insights into the regulatory mechanisms within the healthy and injured periosteum, paving the way for novel translational approaches to bone healing.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.181073","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T12:00:31Z","timestamp":1716465631000},"source":"Crossref","is-referenced-by-count":19,"title":["Endothelial to mesenchymal Notch signaling regulates skeletal repair"],"prefix":"10.1172","volume":"9","author":[{"given":"Sanja","family":"Novak","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, UConn Health, Farmington, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Tanigawa","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, UConn Health, Farmington, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijender","family":"Singh","sequence":"additional","affiliation":[{"name":"Institute for Systems Genomics, Computational Biology Core, UConn, Storrs, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra H.","family":"Root","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, UConn Health, Farmington, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6361-143X","authenticated-orcid":true,"given":"Kurt 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