{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:29:22Z","timestamp":1792182562907,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR202210210042"],"award-info":[{"award-number":["ZR202210210042"]}],"id":[{"id":"10.13039\/501100007129","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":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes play a central role in the pathogenesis of periodontitis, with the Treg\/Th17 (regulatory T cell\/T helper 17 cell) imbalance closely linked to diabetes\u2010associated periodontitis (DPD). Maxacalcitol (OCT), an analog of active vitamin D, has therapeutic effects on diseases involving Treg\/Th17 imbalance. This study aimed to determine whether OCT improved DPD by restoring the Treg\/Th17 imbalance via store\u2010operated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      entry (SOCE)\u2010mediated mitochondrial dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The DPD model was established in male C57BL\/6 mice and treated with local injections or oral administration of OCT. Microcomputed tomography and flow cytometry were used to assess the alveolar bone, Treg\/Th17 balance, and SOCE. Flow cytometry and transmission electron microscopy were applied to detect Treg\/Th17 balance and mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>OCT attenuated alveolar bone loss and Treg\/Th17 imbalance and enhanced the expressions of SOCE components in mice with DPD, with local injections showing more pronounced effects than oral administration. Furthermore, OCT restored the Treg\/Th17 balance and improved mitochondrial dysfunction and overactivation of SOCE caused by lipopolysaccharides and high glucose. Additionally, SOCE inhibitors ameliorated mitochondrial abnormalities and Treg\/Th17 imbalance under DPD conditions, whereas mitochondrial toxin and SOCE activators abolished the beneficial effects of OCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>OCT ameliorates Treg\/Th17 imbalance via SOCE\u2010mediated mitochondrial function, thereby effectively improving DPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      Periodontitis, an inflammatory condition causing bone loss around teeth, is often more severe in individuals with diabetes due to immune system dysfunction. Specifically, diabetes\u2010associated periodontitis (DPD) involves an imbalance between two types of immune cells: regulatory T cells (Treg), which control inflammation, and T helper 17 cells (Th17), which promote inflammation. This study explored how maxacalcitol (1\u03b1,25\u2010dihydroxy\u201022\u2010oxacalcitriol, OCT), a synthetic analog of active vitamin D3, treats DPD by correcting this immune cell imbalance. Using mouse models of DPD, we found that OCT significantly reduced bone loss and restored the balance between Treg and Th17 cells. Further investigation demonstrated that OCT functions by controlling calcium (Ca\n                      <jats:sup>2<\/jats:sup>\n                      \u207a) entry into cells, thereby preserving mitochondrial health. Blocking excessive Ca\n                      <jats:sup>2<\/jats:sup>\n                      \u207a entry confirmed the improvement in immune cell balance. Conversely, increased Ca\n                      <jats:sup>2<\/jats:sup>\n                      \u207a influx or disrupted mitochondrial function negated OCT's beneficial effects. Overall, OCT effectively ameliorates DPD by restoring the Treg\/Th17 balance through alleviating store\u2010operated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      entry (SOCE) overactivation\u2010induced mitochondrial dysfunction, suggesting it could be a promising approach for managing periodontitis in diabetic patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70002","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T06:45:52Z","timestamp":1756881952000},"page":"511-526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Maxacalcitol alleviates diabetes\u2010associated periodontitis in male mice by restoring Treg\/Th17 balance via SOCE\u2010mediated mitochondrial dysfunction"],"prefix":"10.1002","volume":"97","author":[{"given":"Xiaolin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Bone Metabolism School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"},{"name":"Center of Osteoporosis and Bone Mineral Research Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"},{"name":"Center of Osteoporosis and Bone Mineral Research Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"},{"name":"Center of Osteoporosis and Bone Mineral Research Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongrui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"},{"name":"Center of Osteoporosis and Bone Mineral Research Shandong University  Jinan Shandong China"},{"name":"Department of Periodontology School and Hospital of Stomatology Cheeloo College of Medicine Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong China"},{"name":"Center of Osteoporosis and Bone Mineral Research Shandong University  Jinan Shandong China"},{"name":"School of Clinical 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