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.
Ohshima
M
M
Department of Biochemistry, Ohu University School of Pharmaceutical Sciences, Misumido 31-1, Tomitamachi, Koriyama, Fukushima 963-8611, Japan. m-ohshima@pha.ohu-u.ac.jp
Yamaguchi
Y
Y
Matsumoto
N
N
Micke
P
P
Takenouchi
Y
Y
Nishida
T
T
Kato
M
M
Komiyama
K
K
Abiko
Y
Y
Ito
K
K
Otsuka
K
K
Kappert
K
K
D000328:Adult; D007611:Aprotinin / Q000494:pharmacology; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D003470:Culture Media; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D005782:Gels; D005786:Gene Expression Regulation; D005881:Gingiva / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3; D061965:Matrix Metalloproteinase Inhibitors; D010518:Periodontitis / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051900:Smad3 Protein / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D015854:Up-Regulation
D003470:Culture Media; D005782:Gels; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D015842:Serine Proteinase Inhibitors; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen; D007611:Aprotinin; C100342:marimastat; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3