{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:40Z","timestamp":1785405580984,"version":"3.56.0"},"reference-count":82,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006374","name":"Universitas Brawijaya","doi-asserted-by":"crossref","award":["DPA-DALA-121101\/DR2\/2025"],"award-info":[{"award-number":["DPA-DALA-121101\/DR2\/2025"]}],"id":[{"id":"10.13039\/501100006374","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DPA-DALA-121101\/DR2\/2025"],"award-info":[{"award-number":["DPA-DALA-121101\/DR2\/2025"]}],"id":[{"id":"https:\/\/ror.org\/01wk3d929","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fakultas Kedokteran Gigi Universitas Brawijaya","award":["DPA-FKG-331101\/DR2\/2025-3"],"award-info":[{"award-number":["DPA-FKG-331101\/DR2\/2025-3"]}]},{"award":["DPA-FKG-331101\/DR2\/2025-3"],"award-info":[{"award-number":["DPA-FKG-331101\/DR2\/2025-3"]}],"id":[{"id":"https:\/\/ror.org\/01wk3d929","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as \u03b13\u03b21 and \u03b16\u03b24 support barrier integrity, whereas \u03b15\u03b21 may facilitate microbial interaction and inflammatory signaling. \u03b22 integrins and \u03b14\u03b21 contribute to leukocyte recruitment and inflammatory amplification, whereas increased \u03b19\u03b21-associated signaling and reduced \u03b1v\u03b26-mediated regulation of transforming growth factor \u03b2 (TGF-\u03b2) may promote inflammatory persistence. Matrix-associated integrins, including \u03b12\u03b21 and \u03b111\u03b21, support extracellular matrix (ECM) organization and mechanotransduction, whereas \u03b1v\u03b23 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired \u03b21 integrin-dependent signaling and potentially reduced \u03b1v\u03b25-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades.<\/jats:p>","DOI":"10.3390\/biom16070967","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrin Signaling Imbalance in Periodontitis: A Stage-Dependent Link Between Inflammation, Bone Resorption and Regenerative Failure"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1145-0640","authenticated-orcid":false,"given":"Fredy","family":"Mardiyantoro","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universitas Brawijaya, Malang 65145, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-2287","authenticated-orcid":false,"given":"Meircurius Dwi Condro","family":"Surboyo","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4750-4620","authenticated-orcid":false,"given":"Andari","family":"Sarasati","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-1544","authenticated-orcid":false,"given":"Tetsuya","family":"Matsuguchi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universitas Brawijaya, Malang 65145, Indonesia"},{"name":"Department of Oral Biochemistry, Field of Developmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","unstructured":"Gasner, N.S., and Schure, R.S. 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