TGF-{beta} Signaling in Gingival Fibroblast-Epithelial Interaction

Periodical: J Dent Res ISBN: 1544-0591 (Electronic) 0022-0345 (Linking)  Date: 2010/08/27  Language: Eng

Authors:Ohshima, M., Yamaguchi, Y., Matsumoto, N., Micke, P., Takenouchi, Y., Nishida, T., Kato, M., Komiyama, K., Abiko, Y., Ito, K., Otsuka, K., Kappert, K.

A copy of this paper may be available for free: Google Scholar Search 

Abstract
The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-beta has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-beta signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-beta 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-beta-receptor kinase inhibition. Up-regulation of TGF-beta-responsive genes was evident in GF/GE cocultures. Furthermore, the TGF-beta downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-beta signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful model for therapeutic drug screening for periodontitis.in vitro.