{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:30:01Z","timestamp":1773930601738,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Epithelium is the periodontal first line of defense against microbes. Discoidin domain receptor 1 (DDR1) is a collagen receptor expressed in epithelium.\n                      <jats:italic>Ddr1<\/jats:italic>\n                      knockout (\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ) mice develop periodontitis\u2010like defects, including junctional epithelium (JE) downgrowth, bacterial invasion, and alveolar bone loss. The objective of this study was to investigate epithelial responses in the absence of DDR1. We hypothesized that\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice exhibit increased JE permeability and delayed epithelial wound healing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Epithelium was analyzed in\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      and wild\u2010type (\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      ) mice. JE permeability was studied in vivo by applying a fluorescent dye and measuring dye penetration. Immunohistochemistry (IHC) was used to identify the localization of E\u2010cadherin and collagens IV, VIII, and XVII in oral epithelium. DDR1 expression in wound healing was confirmed by histology. Epithelial wound healing responses were assessed by creating skin and oral wounds and measuring epithelial migration and wound closure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No differences in JE permeability were observed between\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice, although a trend in the means was observed toward decreased dye surface area (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.07) and intensity (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.08\u20130.09) in the periodontium of the former mice. IHC did not reveal differences in the localization of E\u2010cadherin or collagens IV, VIII, and XVII between genotypes. In human gingiva,\n                      <jats:italic>DDR1<\/jats:italic>\n                      was expressed at the epithelial front, migrating to cover palatal wounds. Wound healing experiments revealed a higher % wound healing of dorsal skin in\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      than\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice at 5 days post\u2010wounding (dpw) (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DDR1 does not affect JE permeability but may play a role in effective epithelial cell migration during cutaneous wound healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>\n                      Epithelium is the periodontal first line of defense against microbial attacks. Discoidin domain receptor 1 (DDR1) is a collagen receptor expressed at the epithelium. Mice not expressing the receptor (\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice) develop defects consistent with periodontitis, including epithelium downgrowth and bone loss. In this study, we investigated periodontal epithelial permeability by applying a fluorescent dye in the mouth of\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice. Additionally, we used histological methods to reveal differences in the localization of gingival proteins between\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      . Finally, we investigated the role of DDR1 in wound healing in human sections and in a live animal model. No differences in junctional epithelium (JE) permeability were observed between\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice, as expressed by the comparable presence of dye in the periodontal tissues of both types of mice. There were no differences in the localization of E\u2010cadherin or collagens IV, VIII, and XVII between\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      . In human gingiva,\n                      <jats:italic>DDR1<\/jats:italic>\n                      was expressed at the epithelial front, migrating to cover palatal wounds. The animal wound healing study revealed higher healing of skin wounds in\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      than\n                      <jats:italic>\n                        Ddr1\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice at 5 dpw. In conclusion, this study has elucidated a role for DDR1 in epithelial cell migration during skin wound healing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70031","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T04:51:08Z","timestamp":1764737468000},"page":"272-284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Discoidin domain receptor 1 (DDR1) in junctional epithelial permeability and wound healing"],"prefix":"10.1002","volume":"97","author":[{"given":"Christina","family":"Zachariadou","sequence":"first","affiliation":[{"name":"Department of Periodontics and Endodontics School of Dental Medicine University at Buffalo  Buffalo New York USA"},{"name":"Division of Biosciences College of Dentistry The Ohio State University  Columbus Ohio 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