Action Mechanism of FGF-2 on Periodontal Regeneration in Beagle Dogs

Objectives: We have previously demonstrated that fibroblast growth factor-2 (FGF-2) enhanced the neogenesis of alveolar bone, cementum, and periodontal ligament (PDL) in artificial periodontal defect models. However, the action mechanism of FGF-2 on periodontal regeneration in vivo remains unclear. To reveal the action mechanism, formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog three-wall periodontal defect model.
Methods: FGF-2 (0.3%) plus vehicle (hydroxypropyl cellulose:HPC) or vehicle alone (control) was topically applied to the defect. After the application, 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 histologically quantitated. In addition, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time polymerase chain reaction at 7 and 14 days.

Results: Histological analysis revealed that, in comparison with the control, FGF-2 significantly promoted proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days. FGF-2 extended new cementum and PDL at 28 days. The number of blood vessels increased by FGF-2 treatment at 7 days. 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.

Conclusions: Our study revealed three facilitatory mechanisms of FGF-2 on periodontal regeneration. First, FGF-2 accelerated and enhanced the proliferation of the fibroblastic cells derived from bone marrow and PDL for new tissue formation. Second, it enhanced angiogenesis. Finally, it facilitated osteoblast differentiation and bone formation at least in part due to BMP-2 production. Therefore, our study suggests that these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase and lead to enhanced formation of new bone, cementum, and PDL.