RESUMEN
Transforming growth factor beta (TGF beta) has previously been shown to have actions on chondrocytes and cartilage both in vitro and in vivo which suggest a role in connective tissue repair. In particular, some of its actions have been shown to be antagonistic to those of interleukin 1 (IL-1). In this study, the effects of TGF beta on prostaglandin E (PGE) production and caseinase activity, in the presence and absence of IL-1, in human articular chondrocytes were investigated. TGF beta 1 and TGF beta 2 were shown to modulate IL-1 beta-stimulated PGE production and caseinase activity. Both TGF beta 1 and beta 2 inhibited IL-1 beta-stimulated PGE production in the absence of serum and augmented it in the presence of serum. TGF beta 1 and TGF beta 2 inhibited IL-1-stimulated caseinase activity with and without serum. In general, the TGF beta s had little or no effect on basal PGE or caseinase levels. TGF beta s may be important modulators of chondrocyte metabolism, their effects on PGE production may depend on cytokine interactions; furthermore, their effects on caseinase activity may help prevent cartilage breakdown.
Asunto(s)
Cartílago Articular/metabolismo , Interleucina-1/farmacología , Metaloendopeptidasas/metabolismo , Prostaglandinas E/biosíntesis , Factor de Crecimiento Transformador beta/farmacología , Anciano , Anciano de 80 o más Años , Cartílago Articular/citología , División Celular/efectos de los fármacos , División Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Interacciones Farmacológicas , Matriz Extracelular/metabolismo , Humanos , Persona de Mediana Edad , RadioinmunoensayoRESUMEN
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)