{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:04:24Z","timestamp":1784174664087,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7252165"],"award-info":[{"award-number":["7252165"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate whether the hypoxia\u2010inducible factor\u20101alpha (HIF\u20101\u03b1)\/heme oxygenase\u20101 (HO\u20101) axis mediates ferroptosis in periodontal ligament tissues and contributes to impaired periodontal tissue repair in periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      RNA sequencing was performed to identify ferroptosis\u2010related pathways in ligature\u2010induced periodontitis (LIP) model. In\u00a0vivo, LIP and ligature\u2010removal recovery models were treated with the ferroptosis inhibitor Ferrostatin\u20101 (Fer\u20101). Alveolar bone changes were assessed by micro\u2010computed tomography. Osteoclast activity and periodontal ligament\u2013associated repair were evaluated by TRAP staining and Periostin immunohistochemistry. Ferroptosis\u2010related alterations were assessed by immunohistochemistry of HIF\u20101\u03b1, HO\u20101, GPX4, SLC7A11, 4\u2010HNE and Perls staining. In\u00a0vitro, an HIF\u20101\u03b1\u2010activated hPDLSC model was established. Ferroptosis\u2010related changes were evaluated by ROS, MDA, Fe\n                      <jats:sup>2+<\/jats:sup>\n                      levels, C11\u2010BODIPY staining and expression of ferroptosis\u2010associated molecules. The HIF\u20101\u03b1\/HO\u20101 regulatory relationship was examined by ChIP\u2010qPCR and dual\u2010luciferase reporter assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RNA sequencing revealed enrichment of ferroptosis\u2010related pathways and identified HIF\u20101\u03b1 and HO\u20101 as central regulators in inflamed periodontal ligament tissues. In\u00a0vivo, Fer\u20101 attenuated alveolar bone loss, osteoclast activity and inflammatory cell infiltration. These changes were accompanied by decreased HO\u20101 expression, iron deposition and 4\u2010HNE levels, along with increased GPX4 and SLC7A11 expression. In the recovery model, Fer\u20101 further reduced oxidative stress, suppressed osteoclast activity and increased Periostin expression, indicating improved periodontal tissue repair. In\u00a0vitro, HIF\u20101\u03b1 activation was associated with increased Fe\n                      <jats:sup>2+<\/jats:sup>\n                      accumulation, ROS production and ferroptosis\u2010related molecular alterations. Mechanistically, HIF\u20101\u03b1 directly transactivated HO\u20101, which contributed to iron accumulation and downstream ferroptosis\u2010associated changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The HIF\u20101\u03b1\/HO\u20101 signalling axis is associated with ferroptosis\u2010related alterations in the PDL, which constitute periodontal tissue damage and impaired repair in periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcpe.70150","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:46:03Z","timestamp":1780991163000},"page":"1364-1377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HIF<\/scp>\n                    \u20101\u03b1\/\n                    <scp>HO<\/scp>\n                    \u20101 Axis Promotes Ferroptosis and Impairs Periodontal Tissue Repair in Periodontitis"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-6856","authenticated-orcid":false,"given":"Xiaochi","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Periodontology, National Engineering Laboratory for Digital and Material Technology of Stomatology Peking University School and Hospital of Stomatology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-5500","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Periodontology, National Engineering Laboratory for Digital and Material Technology of Stomatology Peking University School and Hospital of Stomatology  Beijing 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