{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T04:23:29Z","timestamp":1793247809319,"version":"4.5.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,23]]},"abstract":"<jats:p>\n                    The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP\u2013Indian hedgehog feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP\n                    <jats:sup>+<\/jats:sup>\n                    resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we specifically activated Hedgehog signaling in PTHrP\n                    <jats:sup>+<\/jats:sup>\n                    resting chondrocytes and traced the fate of their descendants using a tamoxifen-inducible\n                    <jats:italic>Pthrp-creER<\/jats:italic>\n                    line with\n                    <jats:italic>patched-1<\/jats:italic>\n                    \u2013floxed and tdTomato reporter alleles. Hedgehog-activated PTHrP\n                    <jats:sup>+<\/jats:sup>\n                    chondrocytes formed large, concentric, clonally expanded cell populations within the resting zone (\u201c\n                    <jats:italic>patched roses<\/jats:italic>\n                    \u201d) and generated significantly wider columns of chondrocytes, resulting in hyperplasia of the growth plate. Interestingly, Hedgehog-activated PTHrP\n                    <jats:sup>+<\/jats:sup>\n                    cell descendants migrated away from the growth plate and transformed into trabecular osteoblasts in the diaphyseal marrow space in the long term. Therefore, Hedgehog activation drives resting zone chondrocytes into transit-amplifying states as proliferating chondrocytes and eventually converts these cells into osteoblasts, unraveling a potentially novel Hedgehog-mediated mechanism that facilitates osteogenic cell fates of PTHrP\n                    <jats:sup>+<\/jats:sup>\n                    skeletal stem cells.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165619","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T12:01:02Z","timestamp":1701777662000},"source":"Crossref","is-referenced-by-count":25,"title":["Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4226-7358","authenticated-orcid":true,"given":"Shion","family":"Orikasa","sequence":"first","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9577-3249","authenticated-orcid":true,"given":"Yuki","family":"Matsushita","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas, USA."},{"name":"Department of Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Manabe","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fogge","sequence":"additional","affiliation":[{"name":"University of Michigan School of Dentistry, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Lee","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Mizuhashi","sequence":"additional","affiliation":[{"name":"University of Michigan School of Dentistry, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Sakagami","sequence":"additional","affiliation":[{"name":"University of Michigan School of Dentistry, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0358-1897","authenticated-orcid":true,"given":"Wanida","family":"Ono","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas, 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