title: Action Mechanism of Fibroblast Growth Factor-2 (FGF-2) in the Promotion of Periodontal Regeneration in Beagle Dogs.
abstract: Fibroblast growth factor-2 (FGF-2) enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL) in periodontal defect models. However, the mechanism through which FGF-2 acts in periodontal regeneration in vivo has not been fully clarified yet. To reveal the action mechanism, the formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog 3-wall periodontal defect model. FGF-2 (0.3%) or the vehicle (hydroxypropyl cellulose) only were topically applied to the defect in FGF-2 and control groups, respectively. Then, the amount of regenerated tissues and the number of proliferating cells at 3, 7, 14, and 28 days and the number of blood vessels at 7 days were quantitated histologically. Additionally, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time PCR at 7 and 14 days. Compared with the control, cell proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days were significantly promoted by FGF-2. Additionally, the number of blood vessels at 7 days was increased by FGF-2 treatment. At 28 days, new cementum and PDL were extended by FGF-2. Moreover, FGF-2 increased the expression of bone morphogenetic protein 2 (BMP-2) and osteoblast differentiation markers (osterix, alkaline phosphatase, and osteocalcin) in the regenerated tissue. We revealed the facilitatory mechanisms of FGF-2 in periodontal regeneration in vivo. First, the proliferation of fibroblastic cells derived from bone marrow and PDL was accelerated and enhanced by FGF-2. Second, angiogenesis was enhanced by FGF-2 treatment. Finally, osteoblastic differentiation and bone formation, at least in part due to BMP-2 production, were rapidly induced by FGF-2. Therefore, these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase, leading to enhanced formation of new bone, cementum, and PDL.
authors.affiliation: Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., LTD., Kyoto, Kyoto, Japan; Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Nagayasu-Tanaka
authors.affiliation: Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., LTD., Kyoto, Kyoto, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Anzai
authors.affiliation: Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., LTD., Kyoto, Kyoto, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Takaki
authors.affiliation: Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., LTD., Kyoto, Kyoto, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shiraishi
authors.affiliation: Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., LTD., Kyoto, Kyoto, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Terashima
authors.affiliation: Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., LTD., Kyoto, Kyoto, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Nozaki
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004285:Dogs; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010513:Periodontal Ligament / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects*; D014092:Tooth Root / Q000098:blood supply / Q000187:drug effects / Q000473:pathology
chemical_list: D016222:Fibroblast Growth Factor 2