Wasf2: A novel target of intermittent parathyroid hormone administration

Abstract

Systemic intermittent administration of parathyroid hormone (PTH) stimulates bone formation in animals and humans, and recombinant human PTH1-34 (teriparatide) is used clinically for the treatment of osteoporosis. In this study, we investigated the regulation of gene expression by intermittent PTH administration in MC3T3-E1 osteoblastic cells. We found that intermittent PTH1-34 administration downregulated Wiskott-Aldrich syndrome protein family member (Wasf) 2 mRNA expression. Wnt inhibitor, IWP-2, and protein kinase C inhibitor, Go6976, inhibited this downregulation. However, continuous PTH did not affect Wasf2 expression. Transfection of Wasf2 siRNA reduced bone sialoprotein (BSP) mRNA expression in a similar manner following intermittent PTH administration in MC3T3-E1 cells. These results identify Wasf2 as a novel target of intermittent PTH administration via the Wnt and phosphoinositide- dependent protein kinase signaling pathways, and the resulting regulation of BSP expression may contribute to the anabolic effects of PTH.