Simvastatin reduces MMP-3 level in interleukin 1b-stimulated human chondrocyte culture
| Autor: | F Chellini, P.E. Lazzerini, Pier Leopoldo Capecchi, F. Laghi Pasini, Renzo Marcolongo, F Nerucci, M. Piccini, Antonella Fioravanti, Stefania Bisogno |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Simvastatin Immunology Stimulation Osteoarthritis Matrix metalloproteinase General Biochemistry Genetics and Molecular Biology Chondrocyte Chondrocytes Rheumatology Internal medicine Immunology and Allergy Medicine Humans Cells Cultured Interleukin 3 Aged business.industry Interleukin Middle Aged medicine.disease Hydroxymethylglutaryl-CoA reductase Culture Media Extended Report medicine.anatomical_structure Endocrinology Depression Chemical Female Matrix Metalloproteinase 3 Proteoglycans Hydroxymethylglutaryl-CoA Reductase Inhibitors business medicine.drug Interleukin-1 |
| Popis: | Objectives: Matrix metalloproteinases (MMPs) produced by chondrocytes play a role in the development of cartilage degradation in joint diseases. Moreover, inhibition of MMP secretion by macrophages accumulating in arteriosclerotic plaques would account for the plaque stabilising activity of statins in cardiovascular patients. Recently, simvastatin has been shown to inhibit both developing and established collagen induced arthritis in a murine model. We thus decided to investigate the effect of simvastatin on the production of MMP-3 from cultured interleukin (IL)1 stimulated human chondrocytes. Methods: Cells from human cartilage, obtained from eight subjects with osteoarthritis undergoing surgery for total hip prostheses, were cultured in the presence of different concentrations of simvastatin (5, 10, and 50 μmol/l) with and without IL1β (5 ng/ml). MMP-3 level was measured in the culture medium after 48 h of incubation. Results: IL1β stimulation of chondrocytes increased MMP-3 concentration in the cultures (from 0.69 (0.09) to 1.94 (0.12) ng/μg protein). Incubation with simvastatin was associated with a dose dependent reduction in MMP-3 increase, both in the presence (−15%, −17%, and −26% with 5, 10, and 50 μmol/l, respectively) and in the absence (−32% with 50 μmol/l) of IL1β. The inhibiting effect of simvastatin was completely reversed by the addition of mevalonate (100 μmol/l) or farnesol (10 μmol/l). Conclusions: Our data show that simvastatin, by blocking HMGCoA-reductase and interfering in the prenylation processes, is able to inhibit MMP-3 production from cultured human chondrocytes that have been either unstimulated or stimulated with IL1β, thus suggesting a possible additional mechanism for statins in counteracting chronic joint disease related cartilage damage. |
| Databáze: | OpenAIRE |
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