Effects of dexamethasone and celecoxib on calcium homeostasis and expression of cyclooxygenase-2 mRNA in MG-63 human osteosarcoma cells

Clinical and Experimental Rheumatology

C. Perka¹  M. Wiontzek¹  G.-R. Burmester¹  S. Schuchmann¹  F. Buttgereit¹  G. Duda¹  D. Krocker¹  G. Matziolis¹  T. Gaber¹ 

关键词: Osteoblasts;    dexamethasone;    celecoxib;    inflammation;    intracellular Ca2+ concentration;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES: Glucocorticoids and selective COX-2 inhibitors are potent anti-inflammatory agents. They are also suggested to influence bone physiology and remodeling. Here we searched for effects of dexamethasone and celecoxib on crucial parameters of bone physiology that could be therapeutically relevant.METHODS:The human osteosarcoma cell line MG-63 was used to measure effects of these drugs on (i) intracellular calcium concentration ([Ca²⁺]i) using a microfluorometric technique, (ii) alkaline phosphatase and osteocalcin levels (EIA) and (iii) the expression of cox-2 mRNA (quantitative real time PCR). Measurements were performed in Vitamine D-incubated quiescent cells and in cells stimulated with TNF-α and IL-1ΒRESULTS:We found the cytokine-stimulation to increase [Ca²⁺]i which was prevented by dexamethasone already after 30 min and still after 48 h. Dexamethasone was without any effect on [Ca²⁺]i in quiescent cells. Celecoxib had no measurable short-term or long-term effects neither in quiescent nor in stimulated cells. Vitamin D stimulated the expression of cox-2 mRNA which was further enhanced by TNF-α/IL-1Β. Dexamethasone did not have any measurable effects on COX-2 expression after 30 min, but a pronounced inhibition was seen after 48 h. In contrast, celecoxib had no effect on COX-2 expression. Neither of the drugs had any effect on the secretion of alkaline phosphatase and osteocalcin. CONCLUSIONS: We found dexamethasone to inhibit the [Ca²⁺]i increase in MG-63 cells following stimulation and to reduce considerably COX-2 expression via the genomic pathway. In contrast, celecoxib did not show any measurable short-term or long-term effects on the parameters of bone physiology measured.

【 授权许可】

Unknown