The growth‐supportive effect of thrombospondin (TSP1) and the expression of TSP1 by human MG‐63 osteoblastic cells are both inhibited by dexamethasone

FEBS Letters

Delmas, Pierre D.¹  Trzeciak, Marie-Christine³  Clezardin, Philippe¹  Abbadia, Zoher¹  Amiral, Jean² 

[1] INSERM Research Unit 234, Laboratoire de Biochimie des Protéines Osseuses, Pavillon F, Hôpital E. Herriot, Place d'Arsonval, 69437 Lyon Cédex03, France;SERBIO, Gennevilliers, France;Pavillon E, Hôpital Edouard Herriot, Lyon, France

关键词: Thrombospondin;    Dexamethasone;    Proliferation;    Osteoblastic cell;    TSP;    thrombospondin;    BSA;    bovine serum albumin;    PBS;    phosphate-buffered saline;   

DOI  :  10.1016/0014-5793(93)80721-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Thrombospondin (TSP) is a 450-kDa extracellular matrix glycoprotein which supports the growth of human MG-63 osteoblastic cells [Abbadia et al., FEBS Lett., 329 (1993) 341-346]. In this study, we describe the effect of the glucocorticoid, dexamethasone, on cell proliferation and TSP expression by MG-63 cells. Using a serum-free mitogenesis assay, dexamethasone (25 to 500 nM) caused a dose-dependent decrease in [³H]ithymidine incorporation by MG-63 cels in culture, reaching 40% inhibition of cell proliferation at a concentration of 250 nM. Similarly, the stimulatory effect of TSP (500 ) on proliferation of MG-63 cells was totally abolished in the presence of dexamethasone (250 nM). In situ hybridization indicated that TSP mRNA level in dexamethasone-treated MG-63 cells decreased compared to quiescent cells. As judged by fluorescence-activated cell sorting analysis, dexamethasone treatment of MG-63 cells resulted in a 50 to 70% decrease in TSP cell surface expression compared to quiescent cells. Secretion of TSP in the culture fluid of dexamethasone-treated MG-63 cells also decreased by 40% while, under similar experimental conditions, a 180% increase in alkaline phosphatase activity was observed in dexamethasone-treated cells. Because glucocorticoids induce osteoporosis in vivo and reduce proliferation of osteoblasts in vitro, our results argue for an important role of TSP during bone formation.

【 授权许可】

Unknown