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.

• Authors: Pietro Enea Lazzerini, Caterina Capperucci, Adriano Spreafico, Pier Leopoldo Capecchi, Silvia Niccolini, Paolo Ferrata, Bruno Frediani, Mauro Galeazzi, Franco Laghi-Pasini
• Journal: Joint bone spine (Joint Bone Spine) Vol. 80 Issue 2 Pg. 195-200 (Mar 2013) ISSN: 1778-7254 [Electronic] France
• PMID: 22999910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Chemical References

• Culture Media
• Diterpenes
• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• IL6 protein, human
• Interleukin-1beta
• Interleukin-6
• Osteoprotegerin
• Pyrimidines
• RNA, Messenger
• Sulfonamides
• Terpenes
• Farnesol
• Rosuvastatin Calcium
• geranylgeraniol
• Mevalonic Acid

Topics

• Aged
• Bone Resorption (drug therapy, metabolism)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Culture Media (pharmacology)
• Diterpenes (pharmacology)
• Farnesol (pharmacology)
• Femur Head (cytology)
• Fluorobenzenes (pharmacology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Inflammation (drug therapy, metabolism)
• Interleukin-1beta (pharmacology)
• Interleukin-6 (genetics, metabolism)
• Mevalonic Acid (pharmacology)
• Middle Aged
• Osteoblasts (cytology, drug effects, physiology)
• Osteoporosis (drug therapy, metabolism)
• Osteoprotegerin (metabolism)
• Pyrimidines (pharmacology)
• RNA, Messenger (metabolism)
• Rosuvastatin Calcium
• Sulfonamides (pharmacology)
• Terpenes (pharmacology)