Purpose: To determine the osteogenic capacity of combining BMP-2 and a novel growth factor in rabbit bone marrow stromal cells.
Background: Current treatments of complex craniofacial osseous defects are limited by significant morbidity profiles. Tissue engineering solutions offer an alternative to these techniques. Large quantities of BMP are necessary for clinical efficacy resulting in exorbitant cost and undesirable side effects like heterotropic ossification. Oxysterols are osteoinductive cholesterol oxidation products. Synergistic effects of BMP-2 and oxysterol on osteogenic differentiation have been described in murine mesenchymal stem cells (MSCs).
Methods: Rabbit BMSCs were incubated with various concentrations of a novel oxysterol, BMP-2, or a combination at various concentrations. Alkaline phosphatase (ALP) activity was performed. To determine the combination mechanism of action of BMP-2 and oxysterol, rabbit BMSC conditioned with oxysterol and BMP-2 were incubated with a Hedgehog (Hh) inhibitor cyclopamine and ALP activity was measured.
Results: ALP activity in oxysterol treated rabbit BMSCs was higher than in controls and was equivalent to those with BMP-2. ALP activity of rabbit BMSCs treated with the combination was higher than in single drug groups at all concentrations, demonstrating an additive effect of the two growth factors. Cyclopamine negated the positive effect of oxysterol on ALP, but did not decrease this to baseline.
Conclusion: Oxysterols and BMP-2 appear to have an additive effect on osteogenesis in vitro in rabbit BMSCs. This osteogenic activity is in part mediated through the Hh signaling pathway. The combination may allow decreasing the necessary dosage of BMP-2 to achieve osteogenesis.
Conflict of interest : None declared.