{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:39:04Z","timestamp":1793093944908,"version":"4.5.0"},"reference-count":23,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-20-1-0571"],"award-info":[{"award-number":["W81XWH-20-1-0571"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR079367"],"award-info":[{"award-number":["R01AR079367"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE027639"],"award-info":[{"award-number":["R01DE027639"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE029465"],"award-info":[{"award-number":["R01DE029465"]}],"id":[{"id":"10.13039\/100000072","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":[[2026,11]]},"abstract":"<jats:p>\n                    Discoidin Domain Receptor 2 (DDR2) is a collagen-activated tyrosine kinase required for bone and tooth development as well as regeneration of calvarial and long bones. Although DDR2 is expressed in alveolar bone, its functions in this site have not been previously examined. The present study used global and conditional knockout approaches and lineage tracing to examine the functions of DDR2 in alveolar bone formation during tooth socket healing. First molars were extracted from the maxillae of wild-type and globally\n                    <jats:italic toggle=\"yes\">Ddr2<\/jats:italic>\n                    -deficient (\n                    <jats:italic toggle=\"yes\">\n                      Ddr2\n                      <jats:sup>LacZ\/LacZ<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice, and socket healing was measured after 1, 2, or 4\u2009wk. At all times,\n                    <jats:italic toggle=\"yes\">Ddr2<\/jats:italic>\n                    inactivation significantly reduced socket healing. These changes were associated with decreased cell proliferation 3\u2009d after extraction without any detectable changes in apoptosis. In addition, collagen fibril orientation, measured using Picrosirius Red staining under polarized light, was disrupted in tooth sockets from\n                    <jats:italic toggle=\"yes\">Ddr2<\/jats:italic>\n                    -deficient mice. For lineage tracing, 4-wk-old\n                    <jats:italic toggle=\"yes\">\n                      Ddr2\n                      <jats:sup>mer-cre-mer<\/jats:sup>\n                      ; R26R\n                      <jats:sup>tdTomato<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">\n                      Gli1\n                      <jats:sup>CreERT2<\/jats:sup>\n                      ; R26R\n                      <jats:sup>tdTomato<\/jats:sup>\n                    <\/jats:italic>\n                    mice were induced with tamoxifen, first molars were extracted, and socket healing was examined after 1, 3, or 7\u2009d. In both cases, tdTomato+ cells migrated into sockets, where they sequentially co-localized with preosteoblast and osteoblast markers. Thus, both DDR2\n                    <jats:sup>+<\/jats:sup>\n                    and GLI1\n                    <jats:sup>+<\/jats:sup>\n                    cells contribute to socket healing. The considerable overlap observed between DDR2\n                    <jats:sup>+<\/jats:sup>\n                    and GLI1+ cells suggested that DDR2 functioned in GLI1\n                    <jats:sup>+<\/jats:sup>\n                    cells, which are known to have skeletal progenitor properties. Consistent with localization data, conditional knockout (\n                    <jats:italic toggle=\"yes\">\n                      Gli1\n                      <jats:sup>CreERT2<\/jats:sup>\n                    <\/jats:italic>\n                    ;\n                    <jats:italic toggle=\"yes\">\n                      Ddr2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice exhibited reductions in socket healing 1 wk postextraction, although the inhibition of socket repair was less than that seen in global\n                    <jats:italic toggle=\"yes\">Ddr2<\/jats:italic>\n                    knockouts. In summary, this work demonstrates a role for DDR2 in alveolar bone repair, a finding that may have therapeutic implications for the treatment of alveolar bone loss associated with periodontal disease and other disorders.\n                  <\/jats:p>","DOI":"10.1177\/00220345261423834","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:00:00Z","timestamp":1773226800000},"page":"1633-1642","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Discoidin Domain Receptor 2 Is Required for Tooth Extraction Socket Healing"],"prefix":"10.1177","volume":"105","author":[{"given":"R.A.","family":"Kamath","sequence":"first","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"},{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Phanrungsuwan","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Shahid","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Killian","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratory, University of Michigan School of Medicine, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-510X","authenticated-orcid":false,"given":"V.","family":"Kaartinen","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-0576","authenticated-orcid":false,"given":"B.L.","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-2541","authenticated-orcid":false,"given":"R.T.","family":"Franceschi","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"crossref","unstructured":"Ahn S Joyner AL. 2004. Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning. Cell. 118(4):505\u2013516. https:\/\/doi.org\/10.1016\/j.cell.2004.07.023","DOI":"10.1016\/j.cell.2004.07.023"},{"key":"e_1_3_4_3_1","doi-asserted-by":"crossref","unstructured":"Bargal R et al. 2009. Mutations in DDR2 gene cause smed with short limbs and abnormal calcifications. Am J Hum Genet. 84(1):80\u201384. https:\/\/doi.org\/10.1016\/j.ajhg.2008.12.004","DOI":"10.1016\/j.ajhg.2008.12.004"},{"key":"e_1_3_4_4_1","doi-asserted-by":"crossref","unstructured":"Bayer SV et al. 2019. DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in cafs. Elife. 8:e45508. https:\/\/doi.org\/10.7554\/elife.45508","DOI":"10.7554\/eLife.45508"},{"key":"e_1_3_4_5_1","unstructured":"Binrayes A Franceschi RT. 2018. Role of discoidin domain receptor 2 in bone regeneration. J Bone Miner Res. 33(suppl 1):S239. https:\/\/doi.org\/10.1002%2Fjbmr.3621"},{"key":"e_1_3_4_6_1","doi-asserted-by":"crossref","unstructured":"Binrayes A Ge C Mohamed FF Franceschi RT. 2021. Role of discoidin domain receptor 2 in craniofacial bone regeneration. J Dent Res. 100(12):1359\u20131366. https:\/\/doi.org\/10.1177\/00220345211007447","DOI":"10.1177\/00220345211007447"},{"key":"e_1_3_4_7_1","doi-asserted-by":"crossref","unstructured":"Bok S et al. 2023. A multi-stem cell basis for craniosynostosis and calvarial mineralization. Nature. 621(7980):804\u2013812. https:\/\/doi.org\/10.1038\/s41586-023-06526-2","DOI":"10.1038\/s41586-023-06526-2"},{"key":"e_1_3_4_8_1","doi-asserted-by":"crossref","unstructured":"Borochowitz Z et al. 1993. Spondylo-meta-epiphyseal dysplasia (SMED) short limb-hand type: a congenital familial skeletal dysplasia with distinctive features and histopathology. Am J Med Genet. 45(3):320\u2013326. https:\/\/doi.org\/10.1002\/ajmg.1320450308","DOI":"10.1002\/ajmg.1320450308"},{"key":"e_1_3_4_9_1","doi-asserted-by":"crossref","unstructured":"Franceschi RT Hallett SA Ge C. 2023. Discoidin domain receptors; an ancient family of collagen receptors has major roles in bone development regeneration and metabolism. Front Dent Med. 4:1181817. https:\/\/doi.org\/10.3389\/fdmed.2023.1181817","DOI":"10.3389\/fdmed.2023.1181817"},{"key":"e_1_3_4_10_1","doi-asserted-by":"crossref","unstructured":"Fujii S et al. 2023. Bone formation ability of Gli1(+) cells in the periodontal ligament after tooth extraction. Bone. 173:116786. https:\/\/doi.org\/10.1016\/j.bone.2023.116786","DOI":"10.1016\/j.bone.2023.116786"},{"key":"e_1_3_4_11_1","doi-asserted-by":"crossref","unstructured":"Ge C et al. 2016. Discoidin receptor 2 controls bone formation and marrow adipogenesis. J Bone Miner Res. 31(12):2193\u20132203. https:\/\/doi.org\/10.1002\/jbmr.2893","DOI":"10.1002\/jbmr.2893"},{"key":"e_1_3_4_12_1","doi-asserted-by":"crossref","unstructured":"Ge C Li Y Wu F Ma P Franceschi RT. 2023. Synthetic peptides activating discoidin domain receptor 2 and collagen-binding integrins cooperate to stimulate osteoblast differentiation of skeletal progenitor cells. Acta Biomater. 166:109\u2013118. https:\/\/doi.org\/10.1016\/j.actbio.2023.05.039","DOI":"10.1016\/j.actbio.2023.05.039"},{"key":"e_1_3_4_13_1","doi-asserted-by":"crossref","unstructured":"Ge C Mohamed F Binrayes A Kapila S Franceschi RT. 2018. Selective role of discoidin domain receptor 2 in murine temporomandibular joint development and aging. J Dent Res. 97(3):321\u2013328. https:\/\/doi.org\/10.1177\/0022034517738190","DOI":"10.1177\/0022034517738190"},{"key":"e_1_3_4_14_1","doi-asserted-by":"crossref","unstructured":"Kano K et al. 2008. A novel dwarfism with gonadal dysfunction due to loss-of-function allele of the collagen receptor gene DDR2 in the mouse. Mol Endocrinol. 22(8):1866\u20131880. https:\/\/doi.org\/10.1210\/me.2007-0310","DOI":"10.1210\/me.2007-0310"},{"key":"e_1_3_4_15_1","unstructured":"Kopp HG Hooper AT Shmelkov SV Rafii S. 2007. Beta-galactosidase staining on bone marrow. The osteoclast pitfall. Histol Histopathol. 22(9):971\u2013976. https:\/\/doi.org\/10.14670\/hh-22.971"},{"key":"e_1_3_4_16_1","doi-asserted-by":"crossref","unstructured":"Madisen L et al. 2010. A robust and high-throughput cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 13(1):133\u2013140. https:\/\/doi.org\/10.1038\/nn.2467","DOI":"10.1038\/nn.2467"},{"key":"e_1_3_4_17_1","doi-asserted-by":"crossref","unstructured":"Mohamed FF Ge C Binrayes A Franceschi RT. 2020. The role of discoidin domain receptor 2 in tooth development. J Dent Res. 99(2):214\u2013222. https:\/\/doi.org\/10.1177\/0022034519892563","DOI":"10.1177\/0022034519892563"},{"key":"e_1_3_4_18_1","doi-asserted-by":"crossref","unstructured":"Mohamed FF et al. 2022. The collagen receptor discoidin domain receptor 2 functions in Gli1-positive skeletal progenitors and chondrocytes to control bone development. Bone Res. 10(1):11. https:\/\/doi.org\/10.1038\/s41413-021-00182-w","DOI":"10.1038\/s41413-021-00182-w"},{"key":"e_1_3_4_19_1","doi-asserted-by":"crossref","unstructured":"Mohamed FF et al. 2023. Control of craniofacial development by the collagen receptor discoidin domain receptor 2. Elife. 12:e77257. https:\/\/doi.org\/10.7554\/elife.77257","DOI":"10.7554\/eLife.77257"},{"key":"e_1_3_4_20_1","doi-asserted-by":"crossref","unstructured":"Pagani CA et al. 2022. Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization. Sci Adv. 8(51):eabq6152. https:\/\/doi.org\/10.1126\/sciadv.abq6152","DOI":"10.1126\/sciadv.abq6152"},{"key":"e_1_3_4_21_1","doi-asserted-by":"crossref","unstructured":"Wu F et al. 2025. Discoidin domain receptor 2 is an important modulator of BMP signaling during heterotopic bone formation. Bone Res. 13(1):7. https:\/\/doi.org\/10.1038\/s41413-024-00391-z","DOI":"10.1038\/s41413-024-00391-z"},{"key":"e_1_3_4_22_1","doi-asserted-by":"crossref","unstructured":"Yi Y Stenberg W Luo W Feng JQ Zhao H. 2022. Alveolar bone marrow Gli1+ stem cells support implant osseointegration. J Dent Res. 101(1):73\u201382. https:\/\/doi.org\/10.1177\/00220345211013722","DOI":"10.1177\/00220345211013722"},{"key":"e_1_3_4_23_1","doi-asserted-by":"crossref","unstructured":"Zhao H et al. 2015. The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol. 17(4):386\u2013396. https:\/\/doi.org\/10.1038\/ncb3139","DOI":"10.1038\/ncb3139"},{"key":"e_1_3_4_24_1","doi-asserted-by":"crossref","unstructured":"Zhou T Cavalcante RC Ge C Franceschi RT Ma PX. 2025. Synthetic helical peptides on nanofibers to activate cell-surface receptors and synergistically enhance critical-sized bone defect regeneration. Bioact Mater. 43:98\u2013113. https:\/\/doi.org\/10.1016\/j.bioactmat.2024.08.017","DOI":"10.1016\/j.bioactmat.2024.08.017"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345261423834","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345261423834","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345261423834","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345261423834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:29:15Z","timestamp":1793093355000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345261423834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,8]]},"references-count":23,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1177\/00220345261423834"],"URL":"https:\/\/doi.org\/10.1177\/00220345261423834","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,8]]}}}