Regulatory roles of gingival fibroblasts in periodontal homeostasis and inflammatory progression.

OBJECTIVES

To synthesise current evidence on the heterogeneity and functional roles of gingival fibroblasts in periodontal homeostasis and periodontitis progression.

DESIGN

A narrative review was conducted using structured searches of PubMed, Web of Science and CNKI from inception to November 2025, with predefined keywords related to gingival fibroblasts, periodontitis, and periodontal homeostasis.

RESULTS

Evidence indicates that gingival fibroblasts exhibit substantial functional plasticity and subpopulation heterogeneity, as revealed by single-cell and spatial transcriptomic analyses. Under physiological conditions, homeostatic gingival fibroblasts maintain extracellular matrix integrity, support alveolar bone homeostasis, and contribute to immune surveillance. In contrast, during periodontitis, gingival fibroblasts undergo phenotypic transitions toward pro-inflammatory states, characterised by increased secretion of cytokines, upregulation of matrix metalloproteinases, and promotion of osteoclastogenesis. These alterations enhance extracellular matrix degradation and alveolar bone resorption, thereby accelerating disease progression. Emerging evidence further highlights their central role in coordinating immune responses and tissue remodelling within the periodontal microenvironment.

CONCLUSIONS

Gingival fibroblasts are vital orchestrators of periodontal homeostasis and disease. Their phenotypic switching underlies the transition from tissue maintenance to destruction. Targeting fibroblast heterogeneity and function offers a promising avenue for precision diagnostics and regenerative therapies in periodontitis.