{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:51:04Z","timestamp":1791399064041,"version":"4.3.3"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Department of Defense","award":["PW81XWH-21-1-0386"],"award-info":[{"award-number":["PW81XWH-21-1-0386"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institutes of Health","award":["R21 AR076636,R01 AR079246,T32 AR060719,P30 AR074992,S10 RR023660"],"award-info":[{"award-number":["R21 AR076636,R01 AR079246,T32 AR060719,P30 AR074992,S10 RR023660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:p>\n                    Fractures heal by rapid formation of mineralized callus, a process requiring periosteal cell proliferation and differentiation. Our objective was to dissect the contribution of proliferating osteoblast-lineage cells to fracture callus formation. First, mice expressing thymidine kinase (TK) in 3.6Col1a1-lineage cells were treated with ganciclovir (GCV) to ablate proliferating osteolineage cells for 5 or 10 days. Immunostaining demonstrated that this approach specifically depleted TK\n                    <jats:sup>+<\/jats:sup>\n                    proliferating cells in the bony regions of the callus, while sparing other proliferating cells. Single-cell RNA-seq of callus cells revealed that GCV-treated Col1-TK mice had fewer osteoblasts and chondrocytes than controls, with more myofibroblasts and immune cells, consistent with fibrous nonunion. In controls, 15%\u201330% of callus cells expressing the early osteoblast marker Osterix (Osx,\n                    <jats:italic>Sp7<\/jats:italic>\n                    ) and the late marker osteocalcin (Ocn,\n                    <jats:italic>Bglap<\/jats:italic>\n                    ) were in the cell cycle. Next, we targeted proliferating osteolineage cells at different stages of differentiation by crossing Osx-CreERT2, Ocn-Cre, and Dmp1-CreERT2 mice with ROSA-TK mice. Following fracture, each Cre ROSA-TK mouse line exhibited decreased callus bone volume and a shift from callus bone to fibrous tissue. Therefore, during fracture repair, proliferation of callus cells at early and mature stages of osteoblast differentiation is critical to the formation of a mineralized callus that is essential for healing.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.196751","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:00:23Z","timestamp":1788883223000},"source":"Crossref","is-referenced-by-count":0,"title":["Fracture healing requires proliferation of callus cells at early and mature stages of osteoblast differentiation"],"prefix":"10.1172","volume":"11","author":[{"given":"Nicole R.","family":"Gould","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery,"},{"name":"Musculoskeletal Research Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre F.","family":"Coello","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery,"},{"name":"Musculoskeletal Research 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