Regeneration of periodontal tissues by basic fibroblast growth factor

Abstract

Several growth factors (or cytokines) have recently received attention because of their ability to actively regulate various cellular functions of periodontal ligament (PDL) cells and the effects of topical application of such factor(s) on periodontal tissue regeneration has been evaluated. In this study, we examined the role of basic fibroblast growth factor (bFGF) in the wound healing and regeneration of periodontal tissues. Alveolar bone defects (such as 2-wall, 3-wall and furcation class II bone defects) were created surgically in beagle dogs and primates. Recombinant bFGF was topically applied to the artificial bony defects. Six or 8 wk after application, the periodontal regeneration was morphologically and histomorphometrically analyzed. In all sites where bFGF was applied, significant periodontal ligament formation with new cementum deposits and new bone formation was observed in amounts greater than in the control sites. We found it noteworthy that no instances of epithelial down growth, ankylosis or root resorption were observed in the bFGF sites. In vitro studies demonstrated that bFGF enhances the proliferative responses of human PDL cells, which express FGF receptor-1 and -2, but inhibits the induction of alkaline phosphatase activity and mineralized nodule formation by PDL cells. Interestingly, we observed that the mRNA level of laminin in PDL cells, which plays an important role in angiogenesis, was specifically upregulated by bFGF stimulation, but that of type I collagen was downregulated. The present study demonstrates that bFGF can be applied as one of the therapeutic modalities which actively induce periodontal tissue regeneration. The results of in vitro studies suggest that by suppressing the cytodifferentiation of PDL cells into mineralized tissue forming cells, bFGF may play important roles in wound healing by promoting angiogenesis and inducing the growth of immature PDL cells, and may in turn accelerate periodontal regeneration.

Effect of basic fibroblast growth factor on root resorption after delayed autotransplantation of tooth in dogs

“…25, 35-39 FGF-2 has been shown to act on a variety of mesenchymal cell types 40 .With regard to delayed-replantation of tooth, topical application of FGF-2 was shown to be effective in prevention of replacement resorption in animal studies. 22,27 The ability of FGF-2 to stimulate variety of undifferentiated cell types in periodontal tissue 21 lead us to test its potential in enhancing healing of 20 damages induced during the process of autotransplantation. In the present study, significantly greater numbers of PCNA positive cells were found in the newly formed connective tissue in the FGF-2 treated group than in the control group.…”

“…This finding is consistent with the previous report that the types of cell which repopulate the root surface determine the nature of attachment during healing. 44 FGF-2 downregulates alkaline phosphatase activity and reversibly diminishes the PDL cells' potency for mineralized nodule formation 21 . FGF-2 has been shown to suppress the expression of bone-related proteins, such as type I collagen, osteocalcin and bone sialoprotein, but prompted the expression of osteopontin by PDL cells.…”

“…[20][21][22] Basic fibroblast growth factor (bFGF, FGF-2) is a heparin-binding protein with several physiological functions. It is found in ectomesenchyme during the embryonal period.…”

“…[23][24][25] FGF-2 exhibits potent angiogenic activities and mitogenic ability of mesenchymal cells within the PDL. 21 Studies have 7 shown that application of FGF-2 enhances the healing of periodontal tissue without ankylosis, root resorption, or epithelial downgrowth in experimental alveolar bone defects in beagle dogs 21 and primate models. 21,26 Seshima et al 27 reported that FGF-2 promotes formation of new PDL and prevents ankylosis and root resorption following reimplantation of teeth in dogs.…”

“…21 Studies have 7 shown that application of FGF-2 enhances the healing of periodontal tissue without ankylosis, root resorption, or epithelial downgrowth in experimental alveolar bone defects in beagle dogs 21 and primate models. 21,26 Seshima et al 27 reported that FGF-2 promotes formation of new PDL and prevents ankylosis and root resorption following reimplantation of teeth in dogs. Recently, a large-scale multi-center randomized clinical trial in Japan reported that application of FGF-2 is efficacious in the regeneration of human periodontal tissue.…”