THROMBOSPONDIN (TSP1) MEDIATES IN-VITRO PROLIFERATION OF HUMAN MG-63 OSTEOBLASTIC CELLS INDUCED BY ALPHA-THROMBIN

被引:12
作者
ABBADIA, Z
CLEZARDIN, P
SERRE, CM
AMIRAL, J
DELMAS, PD
机构
[1] HOP EDOUARD HERRIOT,INSERM,UR 234,BIOCHIM PROT OSSEUSES LAB,PAVILLON F,PL ARSONVAL,F-69437 LYON 3,FRANCE
[2] SERBIO LABS,GENNEVILLIERS,FRANCE
关键词
THROMBOSPONDIN; THROMBIN; PROLIFERATION; OSTEOBLASTIC CELL;
D O I
10.1016/0014-5793(93)80250-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thrombospondin (TSP) is a 450-kDa glycoprotein synthesized and secreted by human MG-63 osteoblastic cells. In this study, we have first studied the effect of alpha-thrombin on TSP expression by human MG-63 cells. In situ hybridization indicated that TSP mRNA level in thrombin-treated MG-63 cells was increased when compared to unstimulated cells. As judged by immunofluorescence, thrombin-treatment of MG-63 cells resulted in increased cell surface expression of TSP when compared to quiescent cells. Because thrombin stimulates proliferation of osteoblastic cells, the involvement of TSP in proliferation of thrombin-stimulated osteoblastic cells was then investigated using a serum-free mitogenesis assay. Both alpha-thrombin (0.01 to 0.15 U/ml) and TSP (5 to 600 ng/ml) caused a dose-dependent increase in [H-3]thymidine incorporation by MG-63 cells. Proliferation of osteoblastic cells induced by alpha-thrombin or TSP was specifically and totally inhibited by anti-TSP monoclonal antibodies (3-10 mug/ml) or by indomethacin (1 muM), an inhibitor of prostaglandin synthesis. Anti-TSP antibodies which inhibited cell proliferation also inhibit TSP expression to the surface of these cells. Our experiments support the existence of a mechanism whereby TSP bound to the cell surface of thrombin-treated MG-63 cells stimulates secretion of prostaglandins which, in turn, allow cell proliferation to proceed.
引用
收藏
页码:341 / 346
页数:6
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