Rosuvastatin inhibits spontaneous and IL-1β-induced interleukin-6 production from human cultured osteoblastic cells - 30/05/13
, Caterina Capperucci b, Adriano Spreafico b, Pier Leopoldo Capecchi a, Silvia Niccolini b, Paolo Ferrata c, Bruno Frediani b, Mauro Galeazzi b, Franco Laghi-Pasini a
Corresponding author. Department of Clinical Medicine and Immunological Sciences, Division of Clinical Immunology, University of Siena, Policlinico “Le Scotte”, Viale Bracci, Siena, Italy. Tel.: +39 05 77 55 85 743; fax: +39 05 77 23 33 18.Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
Objective |
Experimental and clinical data suggest that statins may protect bone by inhibiting bone resorption and/or stimulating bone formation. Interleukin-6 (IL-6) is produced by osteoblasts, and potently stimulates osteoclast activation playing a key role in normal bone resorption as well as in post-menopausal and inflammation-driven osteoporosis. Although statins inhibit IL-6 production from different cell types, currently no data exist on osteoblasts. The aim of the study was to evaluate the effect of rosuvastatin on IL-6 production by human osteoblasts.
Methods |
Osteoblasts from osteoarthritic patients were incubated with rosuvastatin (0.1–10μmol/L)±IL-1β, and IL-6 production was evaluated as cytokine concentration in the culture medium (ELISA), as well as mRNA expression in the cells (qPCR). Putative intracellular mechanisms of the drug, such as blocking HMG-CoA-reductase, and interference in the prenylation process were investigated by the addition of mevalonate and isoprenoids. The effect of rosuvastatin±IL-1β on the anti-resorptive molecule osteoprotegerin (OPG) was also assessed (ELISA).
Results |
Rosuvastatin significantly reduced IL-6 levels in the osteoblast culture medium, both in unstimulated and IL-1β-stimulated cells. This effect was reversed by mevalonate or geranylgeraniol, but not farnesol. Moreover, the drug decreased both spontaneous and IL-1β-induced IL-6 mRNA expression in osteoblasts. Conversely, rosuvastatin did not affect OPG levels in the culture medium.
Conclusion |
Our results show that rosuvastatin decreases IL-6 production by osteoblasts, thereby suggesting a possible inhibiting activity on osteoclast function in an indirect way. These data may provide further rationale for employing rosuvastatin to beneficially affect bone metabolism in post-menopausal women and possibly in inflammation-driven osteoporosis.
Le texte complet de cet article est disponible en PDF.Keywords : Rosuvastatin, Il-6, Human osteoblasts, Osteoporosis, Inflammation
Plan
Vol 80 - N° 2
P. 195-200 - mars 2013 Retour au numéro
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