Protein geranylgeranylation controls collagenase expression in osteoarthritic cartilage
作者： Francis M. Sverdrup , Matthew P. Yates , Lillian E. Vickery , Jon A. Klover , Lily R.-H. Song
DOI: 10.1016/J.JOCA.2010.03.015
关键词:
摘要: Summary Objective Statins possess anti-inflammatory properties. This study was undertaken to characterize the mechanism of action statin drugs on collagenase expression in primary human osteoarthritic cartilage tissue. Method Human articular chondrocytes and explants from donors were exposed simvastatin presence or absence interleukin-1 beta (IL-1β). Collagenase determined by quantifying levels matrix metalloproteinase 13 (MMP-13) MMP-1 mRNA MMP-13 protein. The tested addition farnesyl pyrophosphate (FPP) geranylgeranyl (GGPP) using inhibitors transferase (FT) (GGT-1). Results Treatment with decreased whether under basal conditions during stimulation IL-1β. protein secreted into culture media also decreased. Genes involved synthesis (type II collagen aggrecan) not down-regulated simvastatin. Exogenous GGPP completely reversed statin-mediated decrease whereas FPP partially effect. An inhibitor GGT-1 mimicked simvastatin-mediated reduction chondrocytes. Finally, consistent impacts expression, as well both blocked type degradation explants. Conclusion These results suggest that statins modulate chondrocyte metabolism reducing prenylation key signaling molecules control collagen-degrading enzymes. Our strongly support hypothesis prenyltransferases including regulate osteoarthritis.
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