Cooperative Effects of FGF-2 and VEGF in Periodontal Ligament Cells
Objectives: We have already demonstrated that topical application of fibroblast growth factor (FGF)-2 enhances periodontal tissue regeneration in both animal models and clinical trials. Although angiogenesis is a very important event for regeneration, the mechanism by which FGF-2 induces angiogenesis in periodontal tissues has not been fully clarified yet. In this study, we investigated whether FGF-2 can induce VEGF (vascular endothelial growth factor) expression in periodontal ligament cells (PDLs) and whether cellular interactions between PDLs and endothelial cells can enhance angiogenesis.
Methods: We used MPDL22(periodontal ligament cells) and b.End5(endothelial cells) which were derived from BALB/c mice. Expressions of VEGF and VEGFR-1(receptor-1) in MPDL22 were examined by RT-PCR, Realtime PCR, ELISA and Western blot. We then examined the effects of VEGF on both proliferation and migration of MPDL22 in the presence or absence of FGF-2 by WST-1 assay and wound healing assay. In addition, we investigated the interaction between MPDL22 and b.End5 for the tube formation.
Results: FGF-2 induced the expression of both VEGF and VEGFR-1 in a dose dependent manner. Co-stimulation with FGF-2 and VEGF increased the proliferation and migration of MPDL22. When MPDL22 were co-cultured with b.End5, the enhanced tube formation was observed. Interestingly, we observed that MPDL22 bound to the tube-forming b.End5 like pericytes. The co-cultured MPDL22 increased the expression of VEGF more than those cultured without endothelial cells and the co-culture-induced tube formation was inhibited by anti-VEGF antibody.
Conclusion: These data suggest that the possibility that local application of FGF-2 induces VEGF expression in PDL and that FGF-2 and VEGF play an important role for inducing angiogenesis, resulting in suitable local environment for the periodontal regeneration at the applied sites. This study was supported by Grant-in Aids from Japan Society for the Promotion of Science(No. 20592427 and No. 20390530 ).
Japanese Division Meeting
2011 Japanese Division Meeting (Hiroshima, Japan) Hiroshima, Japan
2011
Scientific Groups
Kojima, Yuko
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Yanagita, Manabu
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Mori, Kenta
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Yamashita, Motozo
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Nozaki, Takenori
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Yamada, Satoru
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Kitamura, Masahiro
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)
Murakami, Shinya
( Osaka University Graduate School of Dentistry, Suita, Osaka, N/A, Japan
)