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Rosuvastatin inhibits spontaneous and IL-1β-induced interleukin-6 production from human cultured osteoblastic cells.

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 (0.1-10 μmol/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.

journal_name

Joint Bone Spine

journal_title

Joint bone spine

authors

Lazzerini PE,Capperucci C,Spreafico A,Capecchi PL,Niccolini S,Ferrata P,Frediani B,Galeazzi M,Laghi-Pasini F

doi

10.1016/j.jbspin.2012.07.007

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

195-200

issue

2

eissn

1297-319X

issn

1778-7254

pii

S1297-319X(12)00178-9

journal_volume

80

pub_type

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