p73 is essential for Vitamin D mediated osteoblastic differentiation

Abstract

<p>The secosteroid hormone, Vitamin D3, contributes to bone formation, keratinocyte differentiation, and exerts anti-proliferative actions in human cancer through its cognate receptor, the Vitamin D Receptor (VDR). Additionally, treatment of osteosarcoma cells with VD3 induces differentiation by upregulating genes involved in cell cycle arrest and osteoblastic differentiation. Although considerable work has been carried out in understanding the mechanisms underlying VD3 mediated differentiation of human osteosarcoma cells, upstream regulation of the VD3 signaling pathway is still unclear. In this study, we demonstrate that p73, specifically the TAp73alpha isoform, acts as an upstream regulator of VD3 mediated osteoblastic differentiation. We have observed that silencing p73 in osteosarcoma cells leads to a reduction in expression of osteoblastic differentiation markers as well as alkaline phosphatase activity, another marker for differentiation. Additionally, p73 silencing lead to a reduction in VD3 mediated induction of the osteoblastic differentiation markers, OPN and OCN, and alkaline phosphatase. Finally, we have observed that DNA damage in combination with VD3 leads to enhanced osteoblastic differentiation, which was also significantly reduced upon p73 silencing. Taken together, our data suggests a novel role for p73 in vitamin D mediated differentiation of human osteosarcoma cells.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>