Effects of basic fibroblast growth factor on human gingival epithelial cells

Background: Our previous reports found that basic fibroblast growth factor (FGF-2; bFGF) influences the proliferation and extracellular matrix production of periodontal ligament (PDL) cells. In this study, we examined FGF-2 expression in gingival epithelium and the effect of FGF-2 on proliferative responses by gingival epithelial (GE) cells. Methods: Human GE cells were isolated from healthy gingival epithelium, and the mRNA expression of FGF-2 and FGF receptors (FGFRs) was examined by reverse transcription-polymerase chain reaction (RT-PCR). The distribution of FGF-2 in gingival tissues was detected by immunohistological analysis using the monoclonal antibody for human recombinant FGF-2, which was newly established and designated as BF-2. Further, the proliferative responses of GE cells to FGF-2 were investigated by measuring [H-3]-thymidine uptake. Results: RT-PCR revealed that GE cells express FGFR-1, FGFR-2, FGFR-3, and FGFR-4 mRNA; however, not that of FGF-2. Employing immunohistochemical staining with BF-2, FGF-2 was observed localized in the intercellular spaces of gingival epithelium, though not in the cytoplasm of epithelial cells. Interestingly, staining by BF-2 in the intercellular spaces was diminished after treatment of the tissue sections with heparitinase. Further, an in vitro analysis revealed that FGF-2 enhanced the proliferative responses of human GE cells. However, costimulation with fetal calf serum inhibited the FGF-2-induced proliferation of GE cells, whereas the same costimulation synergistically enhanced FGF-2-induced PDL cell proliferation. Conclusions: FGF-2 is anchored in the intercellular spaces of gingival epithelium via heparansulfate and may regulate the growth and cytodifferentiation of GE cells via cell-type specific receptors.