Molecular Basis of Periodontal Tissue Regeneration by FGF-2

Objectives: In this study, we investigated the molecular basis of periodontal tissue regeneration induced by basic fibroblast growth factor (FGF-2). Methods: Furcation class II bone defects were surgically created in beagle dogs and non-human primates and recombinant FGF-2 was topically applied to the artificial bony defects. Six or eight weeks after application, the periodontal regeneration was morphologically and histomorphometrically analyzed. In order to investigate the mechanisms by which periodontal tissue regeneration was induced at the FGF-2-applied sites, in vitro-maintained human periodontal ligament (HPDL) cells were stimulated with FGF-2 and the various cellular functions were examined. Results: In all experimentally-prepared bone defects where FGF-2 was applied, significant periodontal ligament formation with new cementum and new bone formation was observed in amounts greater than in the control sites. No instances of epithelial down growth, ankylosis, or root resorption were observed in the FGF-2-applied sites. In vitro studies demonstrated that FGF-2 enhanced the proliferation of HPDL cells, but inhibits the induction of alkaline phosphatase activity and mineralized nodule formation. Furthermore, we observed that the hyaluronan production of HPDL cells was preferentially upregulated by FGF-2 stimulation, but that collagen production was downregulated. In particular, FGF-2 evokes high molecular hyaluronan by HPDL cells, which promotes wound healing and tissue repair. Conclusion: The present studies suggest that by suppressing the cytodifferentiation of HPDL cells into mineralized tissue forming cells, FGF-2 may play important roles in wound healing by promoting angiogenesis, creating suitable microenvironment, and inducing the growth of immature HPDL cells, and may in turn accelerate periodontal regeneration. It is strongly hoped that a desirable carrier for FGF-2, which provides a formable and osteoconductive scaffold for undifferentiated HPDL cells will be generated in the very near future. Supported by JSPS and the 21st Century COE entitled Origination of Frontier BioDentisry.