{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:54:21Z","timestamp":1777812861641,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30 AR069620"],"award-info":[{"award-number":["P30 AR069620"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 DE11723"],"award-info":[{"award-number":["R01 DE11723"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:p>\n                    Collagen signaling is critical for proper bone and tooth formation. Discoidin domain receptor 2 (DDR2) is a collagen-activated tyrosine kinase receptor shown to be essential for skeletal development. Patients with loss of function mutations in DDR2 develop spondylo-meta-epiphyseal dysplasia (SMED), a rare, autosomal recessive disorder characterized by short stature, short limbs, and craniofacial anomalies. A similar phenotype was observed in Ddr2-deficient mice, which exhibit dwarfism and defective bone formation in the axial, appendicular, and cranial skeletons. However, it is not known if Ddr2 has a role in tooth formation. We first defined the expression pattern of Ddr2 during tooth formation using Ddr2-LacZ knock-in mice. Ddr2 expression was detected in the dental follicle\/sac and dental papilla mesenchyme of developing teeth and in odontoblasts and the periodontal ligament (PDL) of adults. No LacZ staining was detected in wild-type littermates. This Ddr2 expression pattern suggests a potential role in the tooth and surrounding periodontium. To uncover the function of Ddr2, we used Ddr2\n                    <jats:sup>slie\/slie<\/jats:sup>\n                    mice, which contain a spontaneous 150-kb deletion in the Ddr2 locus to produce an effective null. In comparison with wild-type littermates, Ddr2\n                    <jats:sup>slie\/slie<\/jats:sup>\n                    mice displayed disproportional tooth size (decreased root\/crown ratio), delayed tooth root development, widened PDL space, and interradicular alveolar bone defects. Ddr2\n                    <jats:sup>slie\/slie<\/jats:sup>\n                    mice also had abnormal collagen content associated with upregulation of periostin levels within the PDL. The delayed root formation and periodontal abnormalities may be related to defects in RUNX2-dependent differentiation of odontoblasts and osteoblasts; RUNX2-S319-P was reduced in PDLs from Ddr2\n                    <jats:sup>slie\/slie<\/jats:sup>\n                    mice, and deletion of Ddr2 in primary cell cultures from dental pulp and PDL inhibited differentiation of cells to odontoblasts or osteoblasts, respectively. Together, our studies demonstrate odontoblast- and PDL-specific expression of Ddr2 in mature and immature teeth, as well as indicate that DDR2 signaling is important for normal tooth formation and maintenance of the surrounding periodontium.\n                  <\/jats:p>","DOI":"10.1177\/0022034519892563","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T13:29:41Z","timestamp":1577107781000},"page":"214-222","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["The Role of Discoidin Domain Receptor 2 in Tooth Development"],"prefix":"10.1177","volume":"99","author":[{"given":"F.F.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Departments of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Ge","sequence":"additional","affiliation":[{"name":"Departments of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Binrayes","sequence":"additional","affiliation":[{"name":"Departments of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.T.","family":"Franceschi","sequence":"additional","affiliation":[{"name":"Departments of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of 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