Article

Calcified Tissue International

, 85:538

First online:

Biphasic Glucocorticoid-Dependent Regulation of Wnt Expression and Its Inhibitors in Mature Osteoblastic Cells

  • Wendy MakAffiliated withBone Research Program, ANZAC Research Institute, The University of Sydney
  • , Xinyu ShaoAffiliated withBone Research Program, ANZAC Research Institute, The University of SydneyDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes InstituteDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University
  • , Colin R. DunstanAffiliated withBone Research Program, ANZAC Research Institute, The University of SydneyBiomedical Engineering, The University of Sydney
  • , Markus J. SeibelAffiliated withBone Research Program, ANZAC Research Institute, The University of SydneyDepartment of Endocrinology and Metabolism, Concord Hospital and The University of Sydney
  • , Hong ZhouAffiliated withBone Research Program, ANZAC Research Institute, The University of Sydney Email author 

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Abstract

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.

Keywords

Glucocorticoid Osteoblast Wnt Wnt inhibitor Hydroxysteroid dehydrogenase Col2.3-GFP mice