The effect of transforming growth factor beta on the plasminogen activator activity of normal human osteoblast-like cells and a human osteosarcoma cell line MG-63.
Transforming growth beta (TGF-beta) has been proposed to have a role in bone remodeling by affecting the differentiation and activity of osteoblasts and osteoclasts and by inhibiting the production of proteinases, such as plasminogen activators (PAs). Studies on PAs have largely been based on data from nonhuman and fetal cell lines, however. The purpose of this study was to investigate the effect of TGF-beta on the PA activity of normal human osteoblast-like cells and to compare this with its action on the human osteosarcoma cell line MG-63. The action of interleukin-1 beta (IL-1 beta) was also assessed because it has been shown to increase PA activity in other connective tissue cell types. Normal osteoblast-like cells had low to undetectable basal urokinase (uPA) and tissue plasminogen activator (tPA) activity, which was significantly stimulated by TGF-beta 1. This action was shown to be dependent on transcription and new protein synthesis. TGF-beta 2 had a similar action. IL-1 beta did not stimulate PA activity. In contrast, the MG-63 cell line had high basal tPA and uPA activities. TGF-beta 1 decreased basal PA activity, the effect being most marked for uPA activity. IL-1 beta stimulated uPA and tPA activity. TGF-beta 1 inhibited IL-1 beta-stimulated uPA activity, but the effect on tPA was more variable. This study has shown that TGF-beta has opposite effects on the PA activity of the two osteoblast-like cell types studied. Care must therefore be used before extrapolating data from one cell type to another.(ABSTRACT TRUNCATED AT 250 WORDS)
Fawthrop
F W
FW
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, England.
Oyajobi
B O
BO
Bunning
R A
RA
Russell
R G
RG
D016723:Bone Remodeling; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D012516:Osteosarcoma / Q000201:enzymology*; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D007375:Interleukin-1; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D003513:Cycloheximide; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D007213:Indomethacin