Biphasic Glucocorticoid-Dependent Regulation of Wnt Expression and Its Inhibitors in Mature Osteoblastic Cells
Glucocorticoids exert both anabolic and catabolic effects on bone. Previously, we reported that endogenous glucocorticoids control mesenchymal lineage commitment and osteoblastogenesis through regulation of Wnt signaling in osteoblasts. Here, we investigated the effects of glucocorticoids on Wnt expression in mature osteoblasts. Mature osteoblasts and their immature progenitors were separately isolated from Col2.3-GFP transgenic mice in which mature osteoblasts are identifiable through GFP expression. mRNA levels of Wnt2, Wnt2b, Wnt4, Wnt5a, Wnt10b, and Wnt11 were 4- to 12-fold higher in osteoblasts compared to their progenitors (P < 0.05). Expression of Wnt7b and Wnt10b in osteoblasts was modulated by corticosterone (CS), in a biphasic fashion with 3- to 3.5-fold upregulation at 10 nM CS (P < 0.01) and 50% downregulation at 100 nM CS (P < 0.05). CS 100 nM also increased expression of the Wnt inhibitors sFRP-1 and DKK-1 two- to threefold (P < 0.05). We conclude that the contrasting anabolic and catabolic effects of glucocorticoids on bone are, at least in part, mediated through the regulation of Wnt expression and its inhibitors in mature osteoblasts.
KeywordsGlucocorticoid Osteoblast Wnt Wnt inhibitor Hydroxysteroid dehydrogenase Col2.3-GFP mice
We thank Dr. Barbara Kream for providing the Col2.3-11βHSD2 tg mice, Drs. David Rowe and Ivo Kalajzic for the Col2.3-GFP tg mice (both from the University of Connecticut Health Center, Farmington, CT). Our thanks also go to Janine Street and Colette Fong-Yee for their excellent technical assistance and to Mamdouh Khalil and his staff for animal care. This work was supported by the National Health and Medical Research Council, Australia (project grants 402462 and 570946 to H. Z., M. J. S., and C. R. D.).
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