Hedgehog signaling pathway modulates osteogenic differentiation in novel oxysterol-conditioned rabbit bone marrow stromal cells

Purpose: To determine the osteogenic capacity of a novel growth factor on rabbit bone marrow stromal cells.

Background: Current reconstructive techniques for complex craniofacial osseous defects are associated with significant morbidity profiles. Tissue engineering solutions offer an alternative to these techniques. Bone morphogenetic protein (BMP) is an effective osteoinductive growth factor, but its clinical application is limited by exorbitant cost and undesirable side effects. Oxysterols are naturally occurring cholesterol oxidation products that are capable of inducing osteogenic differentiation. The effects of oxysterol on rabbit-bone marrow stromal cells (BMSC) have not been described.

Methods: Rabbit BMSCs were incubated with various concentrations of a novel oxysterol or BMP-2. Alkaline phosphatase (ALP) activity, expression of markers of osteogenic differentiation, and in vitro calcification assays were performed. To determine the mechanism of action of oxysterol, rabbit BMSC conditioned with oxysterol were incubated with various concentrations of the Hedgehog (Hh) inhibitor cyclopamine and ALP activity was measured.

Results: ALP activity in rabbit BMSCs treated with oxysterol was significantly higher than in controls and was equivalent to activity in cells treated with BMP-2. Gene expression of osteogenic markers in BMSCs treated with oxysterol was significantly higher than in control groups. Addition of cyclopamine to cultures negated the positive effect of oxysterol on ALP activity.

Conclusion: Oxysterols can induce osteogenesis in vitro in rabbit BMSCs with an efficacy similar to BMP-2. This is in part mediated through the Hh signaling pathway. Oxysterols may represent a viable alternative to BMP-2 in bone tissue engineering models.

Conflict of interest : None declared.

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Jan 27, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Hedgehog signaling pathway modulates osteogenic differentiation in novel oxysterol-conditioned rabbit bone marrow stromal cells
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