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Simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG‐63 cultures
Author(s) -
RuizGaspa Silvia,
Nogues Xavier,
Enjuanes Anna,
Monllau Joan C.,
Blanch Josep,
Carreras Ramon,
Mellibovsky Leonardo,
Grinberg Daniel,
Balcells Susana,
DíezPerez Adolfo,
PedroBotet Juan
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21259
Subject(s) - osteocalcin , simvastatin , bone morphogenetic protein 2 , osteoblast , atorvastatin , endocrinology , type i collagen , medicine , chemistry , statin , cell culture , cell growth , alkaline phosphatase , biology , biochemistry , in vitro , genetics , enzyme
To clarify the mechanism of the stimulatory effect of statins on bone formation, we have assessed the effect of simvastatin and atorvastatin on osteoblast activity by analysing cell proliferation, as well as collagen, osteocalcin, and bone morphogenetic protein‐2 ( BMP2 ) gene expression in primary human osteoblast (hOB) and MG‐63 cell line cultures. 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 α1 type 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 or atorvastatin at different concentrations. Similar but less significant effects were found on MG‐63 cells. 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 support the bone‐forming effect of statins, probably through the BMP2 pathway. J. Cell. Biochem. 101: 1430–1438, 2007. © 2007 Wiley‐Liss, Inc.