J Appl Biomed 12:127-135, 2014 | DOI: 10.1016/j.jab.2014.02.003

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

Jessica Ann Cottrella, Owen Keaneb, Sheldon Sutton Linc, James Patrick O'Connora,*
a Department of Biochemistry & Molecular Biology, Rutgers University, New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, NJ, United States
b Trinity College, University of Dublin, Dublin, Ireland
c Department of Orthopaedics, Rutgers University, New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, NJ, United States

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.

Keywords: Fracture healing; Recombinant human bone morphogenetic protein-2; Growth factors; Rat; RT-qPCR

Received: June 6, 2013; Revised: October 14, 2013; Accepted: October 17, 2013; Published: July 1, 2014  Show citation

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Cottrell JA, Keane O, Sutton Lin S, O'Connor JP. BMP-2 modulates expression of other growth factors in a rat fracture healing model. J Appl Biomed. 2014;12(3):127-135. doi: 10.1016/j.jab.2014.02.003.
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