Genetic and Molecular Insights into Transforming Growth Factor-Beta Signaling in Periodontitis: A Systematic Review

TL;DR

This review explores how TGF-β signaling, especially TGF-β1, influences periodontitis, showing its potential as a biomarker and therapeutic target.

Contribution

The study systematically reviews TGF-β isoform roles in periodontitis, highlighting TGF-β1's consistent elevation and potential diagnostic value.

Findings

TGF-β1 is consistently elevated in diseased gingival tissue and fluid, correlating with disease severity.

Post-treatment reductions in TGF-β suggest its potential as a dynamic biomarker for periodontitis.

TGF-β signaling is linked to immune modulation, fibrosis, bone turnover, and systemic comorbidities.

Abstract

Background/Objectives: Transforming growth factor-beta (TGF-β) 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-β 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-β 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-β1 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-β, supporting its value as a dynamic biomarker. Additional findings linked TGF-β signaling to immune modulation, fibrosis, bone turnover, and systemic comorbidities. Evidence for TGF-β2 and TGF-β3 was limited but suggested isoform-specific roles in epithelial–mesenchymal signaling and scar-free repair. Conclusions: Current evidence supports TGF-β, particularly TGF-β1, 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.

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