The phenotypic modulation of fibroblasts and its application for periodontal therapy

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In this study, we developed a culture system in which fibroblasts express alkaline phosphatase (ALP), in order to understand the phenotypic modulation of fibroblasts and its application for the periodontal tissue-engineering therapy. Ascorbic acid (AsA) induced ALP activity and protein in human gingival fibroblasts in conventional monolayer culture. Transforming growth factor-β (TGF-β) at high doses caused cell growth and inhibited the up-regulation by AsA of ALP activity, whereas the low doses promoted ALP induction without stimulating proliferation. Exposure of cells in monolayer to the medium supplemented with AsA, high TGF-β levels, and 10% serum resulted in the formation of multilayers. Transfer of these multilayers to the medium containing AsA and low TGF-β levels caused a marked up-regulation of ALP activity. These results demonstrate that a combination of AsA and TGF-β promoted multilayer formation and ALP induction in fibroblasts. Our results suggest a possible application of fibroblast phenotypic modulation for the periodontal tissue-engineering therapy.