Simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG‐63 cultures

Toclarifythemechanismofthestimulatoryeffectofstatinsonboneformation,wehaveassessedtheeffect of simvastatin and atorvastatin on osteoblast activity by analysing cell proliferation, as well as collagen, osteocalcin, and bone morphogeneticprotein-2(BMP2)geneexpression inprimary humanosteoblast(hOB)andMG-63 celllinecultures. Explants of bone from patients without any metabolic disease under orthopedic hip procedures were used to obtain hOB. Cell cultures were established, synchronized, and different concentrations of simvastatin or atorvastatin were added (10 � 9 M, 10 � 8 M, 10 � 7 M, 10 � 6 M) during the experiment. Cell proliferation was analyzed after 24 h. Collagen polypeptide a 1t ype 1( COL1A1) gene expression, osteocalcin, and BMP2 expression levels were quantified by real-time PCR after 24 h incubation with statins. There was a statistically significant decrease in cell proliferation related to simvastatin or atorvastatin addition at all concentrations in primary hOB compared with those not treated. A significant increase in COL1A1, osteocalcin, and BMP2 gene expression was detected when hOB cultures were treated with simvastatin oratorvastatinatdifferentconcentrations.SimilarbutlesssignificanteffectswerefoundonMG-63cells.After statin treatment we observed both an arrest of proliferation in hOB cells and an increase in collagen, osteocalcin, and BMP2 gene expression, consistent with a stimulatory effect towards mature osteoblast differentiation. These findings supportthebone-formingeffectofstatins,probablythroughtheBMP2pathway.J.Cell.Biochem.101:1430-1438,2007. 2007 Wiley-Liss, Inc.