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.
Highlights
Regeneration of periodontal tissue is the ultimate goal of periodontal therapy
We have demonstrated that fibroblast growth factor-2 (FGF-2) enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL), resulting in the induction of balanced periodontal tissue regeneration in artificial periodontal defect models in the beagle dog [11, 12] and non-human primates [13]
This study presents a detailed qualitative analysis of periodontal regeneration induced by FGF2 in the early regeneration phase
Summary
No conventional periodontal and/or surgical treatment can regenerate lost periodontal tissue or its functionality. We have been investigating the induction of periodontal regeneration by topical application of fibroblast growth factor-2 (FGF-2). We have demonstrated that FGF-2 enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL), resulting in the induction of balanced periodontal tissue regeneration in artificial periodontal defect models in the beagle dog [11, 12] and non-human primates [13]. To reveal the action mechanism of FGF-2 in periodontal regeneration, we conducted two investigations using a beagle dog 3-wall periodontal defect. We revealed that FGF-2 stimulated proliferative responses and angiogenesis and increased the expression of several osteogenic differentiation markers in the regenerated tissue
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