{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:20:25Z","timestamp":1774329625862,"version":"3.50.1"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,3,13]]},"abstract":"<jats:p>Mdm2 is required to negatively regulate p53 activity at the peri-implantation stage of early mouse development. However, the absolute requirement for Mdm2 throughout embryogenesis and in organogenesis is unknown. To explore Mdm2\u2013p53 signaling in osteogenesis, Mdm2-conditional mice were bred with Col3.6-Cre\u2013transgenic mice that express Cre recombinase in osteoblast lineage cells. Mdm2-conditional Col3.6-Cre mice die at birth and display multiple skeletal defects. Osteoblast progenitor cells deleted for Mdm2 have elevated p53 activity, reduced proliferation, reduced levels of the master osteoblast transcriptional regulator Runx2, and reduced differentiation. In contrast, p53-null osteoprogenitor cells have increased proliferation, increased expression of Runx2, increased osteoblast maturation, and increased tumorigenic potential, as mice specifically deleted for p53 in osteoblasts develop osteosarcomas. These results demonstrate that p53 plays a critical role in bone organogenesis and homeostasis by negatively regulating bone development and growth and by suppressing bone neoplasia and that Mdm2-mediated inhibition of p53 function is a prerequisite for Runx2 activation, osteoblast differentiation, and proper skeletal formation.<\/jats:p>","DOI":"10.1083\/jcb.200508130","type":"journal-article","created":{"date-parts":[[2006,3,13]],"date-time":"2006-03-13T20:08:11Z","timestamp":1142280491000},"page":"909-921","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":226,"title":["Osteoblast differentiation and skeletal development are regulated by Mdm2\u2013p53 signaling"],"prefix":"10.1083","volume":"172","author":[{"given":"Christopher J.","family":"Lengner","sequence":"first","affiliation":[{"name":"1Department of Cell Biology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather A.","family":"Steinman","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Gagnon","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Smith","sequence":"additional","affiliation":[{"name":"2Department of Pathology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet E.","family":"Henderson","sequence":"additional","affiliation":[{"name":"4Department of Medicine, McGill University, Montreal, Quebec H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara E.","family":"Kream","sequence":"additional","affiliation":[{"name":"5Department of Medicine and Genetics and"},{"name":"6Department of Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary S.","family":"Stein","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane B.","family":"Lian","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen N.","family":"Jones","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology,"},{"name":"3Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2006,3,13]]},"reference":[{"key":"2023072907172277500_BIB1","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/emboj\/cdg133","volume":"22","year":"2003","journal-title":"EMBO J."},{"key":"2023072907172277500_BIB2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/S0960-9822(95)00183-7","volume":"5","year":"1995","journal-title":"Curr. 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