{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:13:47Z","timestamp":1792030427055,"version":"4.4.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Transforming growth factor-beta (TGF-\u03b2) is a multifunctional cytokine involved in immune regulation, extracellular matrix turnover, and tissue repair. Its role in periodontitis remains controversial due to conflicting human studies. This systematic review addressed the PICO-based question: in adults with periodontitis (population), how does the expression and regulation of TGF-\u03b2 isoforms (intervention\/exposure) compare with healthy or post-treatment states (comparator) regarding clinical outcomes (outcomes)? Methods: A systematic search of PubMed and Scopus was conducted on 1 July 2025 for human studies published in English between 2010 and 2025. Eligible studies investigated TGF-\u03b2 expression, function, or genetic regulation in periodontal tissues or biological fluids. Screening and quality appraisal were performed according to PRISMA guidelines, using design-specific risk-of-bias tools. The review protocol was prospectively registered in PROSPERO (CRD420251138456). Results: Fifteen studies met inclusion criteria. TGF-\u03b21 was the most frequently analyzed isoform and was consistently elevated in diseased gingival tissue and gingival crevicular fluid, correlating with probing depth and attachment loss. Several studies reported post-treatment reductions in TGF-\u03b2, supporting its value as a dynamic biomarker. Additional findings linked TGF-\u03b2 signaling to immune modulation, fibrosis, bone turnover, and systemic comorbidities. Evidence for TGF-\u03b22 and TGF-\u03b23 was limited but suggested isoform-specific roles in epithelial\u2013mesenchymal signaling and scar-free repair. Conclusions: Current evidence supports TGF-\u03b2, particularly TGF-\u03b21, as a central mediator of periodontal inflammation and repair, with promise as both a biomarker and therapeutic target. Standardized, isoform-specific, and longitudinal studies are needed to clarify its diagnostic and translational utility.<\/jats:p>","DOI":"10.3390\/genes16101165","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:06:02Z","timestamp":1759316762000},"page":"1165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic and Molecular Insights into Transforming Growth Factor-Beta Signaling in Periodontitis: A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Tomasz","family":"Paw\u0142aszek","sequence":"first","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"},{"name":"PROTOM Dental, 32-500 Chrzan\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-7145","authenticated-orcid":false,"given":"Beniamin Oskar","family":"Grabarek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Isola, G., Polizzi, A., Serra, S., Boato, M., and Sculean, A. 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