title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Clinical Medicine and Immunological Sciences, Division of Clinical Immunology, University of Siena, Policlinico Le Scotte, Viale Bracci, Siena, Italy. lazzerini7@unisi.it
authors.forename: Pietro Enea
authors.initials: PE
authors.lastname: Lazzerini
authors.forename: Caterina
authors.initials: C
authors.lastname: Capperucci
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Niccolini
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferrata
authors.forename: Bruno
authors.initials: B
authors.lastname: Frediani
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
mesh_terms: D000368:Aged; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology; D005270:Femur Head / Q000166:cytology; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008798:Mevalonic Acid / Q000494:pharmacology; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology
chemical_list: D003470:Culture Media; D004224:Diterpenes; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D053244:Osteoprotegerin; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D013729:Terpenes; D005204:Farnesol; D000068718:Rosuvastatin Calcium; C017338:geranylgeraniol; D008798:Mevalonic Acid