BMP-2 modulates expression of other growth factors in a rat fracture healing model

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteo-inductive reagent that can be used therapeutically to promote spinal arthrodesis and fracture healing. Despite its clinical use, the effect of rhBMP-2 on expression of endogenous osteogenic growth factors is poorly described. The goal of this study was to determine if local rhBMP-2 treatment modulates expression of pro-osteogenic growth factors during fracture healing. Rat femur fractures were wrapped with control or rhBMP-2 collagen soaked sponge. Radiographic observations demonstrated that rhBMP-2 treatment enhanced fracture callus formation and decreased bridging time. Expression of fracture site growth factor mRNAs was determined by quantitative polymerase chain reaction. The gene expression data demonstrated that rhBMP-2 treatment significantly increased mRNA levels of BMP-2 at day 4, BMP-4 at days 2, 4, 7, and 10, BMP-7 at day 2, and TNF-α at day 7. Treatment with rhBMP-2 was shown to significantly reduce mRNA levels of BMP-2 on day 2 and 10, TNF-α on day 14, and BMP-6 on days 2, 10, 14, and 21. TGFβ-1 was also significantly reduced on days 2 and 21. In conclusion, treatment with rhBMP-2 appears to enhance expression of other osteogenic factors that could contribute to bone formation.