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FGF-2 and BMPs are expressed simultaneously during the embryonic bone development and repair of fractured bone. Delivery of BMP-2 peptide and gene has been evaluated for a therapeutic bone regeneration. However, low efficacy and short half -life of BMP-2 peptide have limited their clinical uses. This study was to determine the effects of BMP-2 and FGF-2 combination on bone formation with the adenoviral BMP-2 and FGF-2 gene delivery. Adenoviruses (Ad) expressing BMP-2 or FGF-2 were constructed under the CMV promoter, and characterized. AdBMP-2 dose-dependantly induced BMP-2 peptide expression in BLK cells, and increased alkaline phosphatase (ALP) activity in C2C12. AdFGF-2 also induced FGF-2 peptide expression in a dose-dependent manner. Proliferation of C3H10T1/2, ST-2 and MC3T3-E1 cell was stimulated by AdFGF-2 alone treatment, but ALP activity of the cells was inhibited. To evaluate the effect of BMP-2 and FGF-2 combination on bone formation, AdBMP-2 (100 moi) and/or AdFGF-2 (100 or 200 moi) were transduced into BLK fibroblast cells, and then the cells were transferred into subcutaneous spaces with collagen hydrogel in mice. Microradiographic analysis, biochemical assays and histology showed AdBMP-2 and AdFGF-2 combination produced less bone than AdBMP-2 alone at 2 weeks after implantation. In addition, AdBMP-2/AdFGF-2 combination group had less ALP activity and concentrations of inorganic phosphate and calcium in implants than AdBMP-2 treated group. These results suggest that FGF-2 may stimulate the proliferation of osteoblastic cells, but inhibit the BMP-2 induction of osteoblast differentiation and bone formation.


FGF-2 and BMPs are expressed simultaneously during the embryonic bone development and repair of fractured bone. Delivery of BMP-2 peptide and gene has been evaluated for a therapeutic bone regeneration. However, low efficacy and short half -life of BMP-2 peptide have limited their clinical uses. This study was to determine the effects of BMP-2 and FGF-2 combination on bone formation with the adenoviral BMP-2 and FGF-2 gene delivery. Adenoviruses (Ad) expressing BMP-2 or FGF-2 were constructed under the CMV promoter, and characterized. AdBMP-2 dose-dependantly induced BMP-2 peptide expression in BLK cells, and increased alkaline phosphatase (ALP) activity in C2C12. AdFGF-2 also induced FGF-2 peptide expression in a dose-dependent manner. Proliferation of C3H10T1/2, ST-2 and MC3T3-E1 cell was stimulated by AdFGF-2 alone treatment, but ALP activity of the cells was inhibited. To evaluate the effect of BMP-2 and FGF-2 combination on bone formation, AdBMP-2 (100 moi) and/or AdFGF-2 (100 or 200 moi) were transduced into BLK fibroblast cells, and then the cells were transferred into subcutaneous spaces with collagen hydrogel in mice. Microradiographic analysis, biochemical assays and histology showed AdBMP-2 and AdFGF-2 combination produced less bone than AdBMP-2 alone at 2 weeks after implantation. In addition, AdBMP-2/AdFGF-2 combination group had less ALP activity and concentrations of inorganic phosphate and calcium in implants than AdBMP-2 treated group. These results suggest that FGF-2 may stimulate the proliferation of osteoblastic cells, but inhibit the BMP-2 induction of osteoblast differentiation and bone formation.