TGF-β signaling in gingival fibroblast-epithelial interaction.

The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-β has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-β signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-β inhibition. A novel three-dimensional (3D) gel-culture system consisting of primary human gingival fibroblasts (GF) and gingival epithelial (GE) cells in collagen gels was applied. GF populations from patients with severe periodontitis degraded collagen gels, which was reduced by TGF-β-receptor kinase inhibition. Up-regulation of TGF-β-responsive genes was evident in GF/GE co-cultures. Furthermore, the TGF-β downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-β signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful in vitro model for therapeutic drug screening for periodontitis.