Modulation of Dickkopf-1 Attenuates Glucocorticoid Induction of Osteoblast Apoptosis, Adipocytic Differentiation, and Bone Mass Loss

• DOI: 10.1210/en.2007-0910
• Publication Date: 2008-01-04T01:34:09Z
• Authors: Feng-Sheng Wang; Jih-Yang Ko; Da-Wei Yeh; Huei-Ching Ke; Hsing-Long Wu
• Keywords: DKK1

Long-term glucocorticoid treatment impairs the survival and bone formation of osteogenic cells, leading to mass loss. The Wnt inhibitor Dickkopf-1 (DKK1) acts as a potent bone-remodeling factor that mediates several types skeletal disorders. Whereas excess is known disturb signaling in modulation skeletally deleterious effects DKK1 alleviate induction loss has not been tested. In this study, knockdown expression by end-capped phosphorothioate antisense oligonucleotide (DKK1-AS) abrogated dexamethasone suppression alkaline phosphatase activity osteocalcin MC3T3-E1 preosteoblasts. Exogenous DKK1-AS alleviated mineral density, trabecular volume, osteoblast surface, rate tissue ex vivo osteogenesis primary bone-marrow mesenchymal cells. inhibited adipocyte volume marrow cavity steroid-treated tissue. Immunohistochemical observation revealed dexamethasone-induced terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling osteoblasts adjacent bone. Knocking down dexamethasone-modulated nuclear β-catenin phosphorylated Ser473-Akt adipocytic differentiation progenitor cell cultures. Taken together, knocking effect on microstructure. appeared protect modulating Akt-mediated well adipogenic activities glucocorticoid-stressed osteoprogenitor Interference with osteogenesis-inhibitory action therapeutic potential for preventing osteopenia.