{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:49:14Z","timestamp":1791866954193,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE0346595"],"award-info":[{"award-number":["R01DE0346595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AR069620"],"award-info":[{"award-number":["P30AR069620"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K12DE027826"],"award-info":[{"award-number":["K12DE027826"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32DE007057"],"award-info":[{"award-number":["T32DE007057"]}],"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"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alveolar bone loss is the hallmark of periodontitis and often remains refractory to conventional mechanical and antimicrobial therapies in chronic cases. Mer receptor tyrosine kinase (Mertk) has been implicated in bone homeostasis, yet the immune mechanisms by which Mertk modulates periodontal bone resorption remain insufficiently characterized. The aim of this study is to investigate the role of Mertk deficiency in modulating the inflammatory response during ligature\u2010induced periodontitis and its impact on alveolar bone loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J wild\u2010type (WT) and Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      mice at 6\u2010 to 8\u2010weeks\u2010old were assigned to two experimental groups, the healthy control and ligated. Eight WT and eight Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      mice received a 5\u20130 braided silk ligature around the left second maxillary molar for 7 days to induce experimental periodontitis. The remaining mice were used as healthy controls. Alveolar bone loss was measured morphometrically, and each condition used five mice. Immune cell populations were characterized by flow cytometry. Neutrophil reactive oxygen species (ROS) production was assessed by in vivo luminol imaging, and degranulation was evaluated ex vivo following PMA stimulation. The presence of osteoclasts in sulcular tissues was quantified using TRAP staining. A minimum of three mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u2265 3) were used in all experiments. The results were compared using two\u2010way ANOVA followed by Tukey's multiple comparison correction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At a healthy baseline, Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      mice showed significantly shorter alveolar bone crest to CEJ distances than WT controls (0.174\u00a0\u00b1\u00a00.005\u00a0mm WT, 0.146\u00a0\u00b1\u00a00.012\u00a0mm Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). When presented with ligature\u2010induced periodontitis, Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      mice demonstrated significantly reduced alveolar bone loss compared with WT controls (0.065\u00a0\u00b1\u00a00.019\u00a0mm vs. 0.122\u00a0\u00b1\u00a00.005\u00a0mm;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Neutrophil proportions increased in both groups following ligation (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001), though Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      mice had higher baseline neutrophil levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and elevated baseline B\u2010cell proportions (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Under ligated conditions, Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      neutrophils produced significantly less ROS (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05), and PMA\u2010induced degranulation was reduced in Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      neutrophils from healthy mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). TRAP staining revealed 28% fewer osteoclasts in Mertk\n                      <jats:sup>\u2212\u2216\u2212<\/jats:sup>\n                      sulcular tissues versus WT following ligation (89\u00a0\u00b1\u00a07\u00a0vs. 123\u00a0\u00b1\u00a09 per section;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genetic ablation of Mertk attenuates alveolar bone resorption in experimental periodontitis by modulating neutrophil function and reducing osteoclast recruitment. This research identifies Mertk as a potential target for preserving alveolar bone in periodontal disease and supports further preclinical evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Periodontitis causes inflammation that destroys the bone supporting teeth, and current treatments do not always stop this bone loss. In mice, removing Mertk signaling reduced bone loss by changing the activity of inflammation\u2010fighting cells and decreasing the number of cells that break down bone. These findings suggest that blocking Mertk could offer a new way to preserve bone in people with periodontal disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70202","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:37:54Z","timestamp":1791866274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mertk drives alveolar bone loss in experimental periodontitis associated with altered neutrophil function and osteoclast recruitment"],"prefix":"10.1002","author":[{"given":"Nicholas","family":"Mazzara","sequence":"first","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan 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