Effects of basic fibroblast growth factor on the remodeling of alveolar bone

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In order to maintain the healthy periodontal tissue, adequate supportive alveolar bone volume is required. Continuous bone remodeling is regulated by orchestrated cellular functions between osteoblasts and osteoclasts in periodontal tissue. On the other hand, we have already demonstrated that topical application of fibroblast growth factor-2 (FGF-2) induced significant periodontal tissue regeneration.In this study, we examined the effects of FGF-2 on osteoclastogenesis in periodontal tissues. Immunohistochemical analysis revealed that FGF-2 is distributed on the periodontal ligament cells, gingival fibroblasts and osteoclasts in the periodontal tissue of beagle dogs with naturally occurring periodontitis. In in vitro studies, we successfully induced multinucleated osteoclasts from murine myelomonocytic cells (RAW264) by stimulating the cells with soluble RANKL (receptor activator of NF-κB ligand) for 3 days. Furthermore, we demonstrated that FGF-2 had no direct effects on the osteoclast formation from RAW264 cells under the stimulation with soluble RANKL. Interestingly, however, the conditioned medium of FGF-2-stimulated murine clonal periodontal ligament cells (MPDL-22) and gingival fibroblasts (MG/B6) showed the inhibitory effects on the osteoclast formation, but did not influence the maturation of the osteoclasts. This inhibitory effect was restored by the pretreatment of conditioned medium with anti-OPG (osteoprotegerin) mAb. In addition, FGF-2 upregulated the OPG and RANKL mRNA expressions in MPDL-22 and MG/B6. These results suggest that FGF-2-induced OPG produced from periodontal tissue cells can inhibit osteoclast formation in the periodontal tissue and may in turn support the alveolar bone formation.