PMID: 19947171Dec 2, 2009Paper

Inhibitory effects of pharmacological doses of dexamethasone on mineralization of mesenchymal progenitor cells in vitro

Die Pharmazie
Jin ShaoLianfu Deng

Abstract

Dexamethasone (Dex), a synthetic glucocorticoid, has a clinical adverse effect on bone acquisition and metabolism at pharmacological doses. To investigate the underlying mechanisms of Dex induced bone loss, we employed calvaria derived mesenchymal progenitor cells (MPCs) to examine the effects of Dex on their osteoblast lineage commitment and mineralization function. MPCs were cultured up to 28 days in the presence or absence of pharmacological doses of Dex. Alkaline phosphatase (ALP) and von Kossa histochemical staining showed that Dex decreased ALP activity and mineralized nodule formation. In addition, Dex treatment led to inhibition of cell proliferation and a decrease of cell numbers as assessed by BrdU incorporation and MTT methods, while it increased apoptosis as shown by flow cytometry of annexin V-stained cells. These effects were associated with a marked reduction of secreted IGF-I levels as indicated by ELISA quantification, raising the possibility that Dex decreased proliferation and promoted apoptosis of MPCs through the inhibition of IGF-I secretion. To further define the effect of Dex on osteoblast lineage commitment, Runx2 and Osx, the key transcription regulators of osteogenesis, were determined at both mRNA an...Continue Reading

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