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Atorvastatin stimulates the production of osteoprotegerin by human osteoblasts.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2005 Dec 15; Vol. 96 (6), pp. 1244-53. - Publication Year :
- 2005
-
Abstract
- Recently, HMG-CoA reductase inhibitors (statins), potent inhibitors of cholesterol biosynthesis, have been linked to protective effects on bone metabolism. Because of their widespread use, prevention of bone loss and fractures would be a desirable side effect. However, the mechanisms how statins may affect bone metabolism are poorly defined. Here, we evaluated the effect of atorvastatin on osteoblastic production of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG), cytokines that are essential for osteoclast cell biology. While RANKL enhances osteoclast formation and activation, thereby, promoting bone loss, OPG acts as a soluble decoy receptor and antagonizes the effects of RANKL. In primary human osteoblasts (hOB), atorvastatin increased OPG mRNA levels and protein secretion by hOB by up to three fold in a dose-dependent manner with a maximum effect at 10(-6) M (P < 0.001). Time course experiments indicated a time-dependent stimulatory effect of atorvastatin on OPG mRNA levels after 24 h and on OPG protein secretion after 48-72 h (P < 0.001). Treatment of hOB with substrates of cholesterol biosynthesis that are downstream of the HMG-CoA reductase reaction (mevalonate, geranylgeranyl pyrophosphate) reversed atorvastatin-induced enhancement of OPG production. Of note, atorvastatin abrogated the inhibitory effect of glucocorticoids on OPG production. Treatment of hOB with atorvastatin enhanced the expression of osteoblastic differentiation markers, alkaline phosphatase and osteocalcin. In summary, our data suggest that atorvastatin enhances osteoblastic differentiation and production of OPG. This may contribute to the bone-sparing effects of statins.<br /> (Copyright 2005 Wiley-Liss, Inc.)
- Subjects :
- Adult
Atorvastatin
Cell Differentiation drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Female
Glucocorticoids metabolism
Glucocorticoids pharmacology
Glycoproteins drug effects
Glycoproteins metabolism
Heptanoic Acids metabolism
Humans
Male
Mevalonic Acid metabolism
Models, Biological
Osteoblasts drug effects
Osteoprotegerin
Pyrroles metabolism
RNA, Messenger drug effects
RNA, Messenger metabolism
Receptors, Cytoplasmic and Nuclear drug effects
Receptors, Cytoplasmic and Nuclear metabolism
Receptors, Tumor Necrosis Factor drug effects
Receptors, Tumor Necrosis Factor metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Glycoproteins biosynthesis
Heptanoic Acids pharmacology
Osteoblasts metabolism
Pyrroles pharmacology
Receptors, Cytoplasmic and Nuclear biosynthesis
Receptors, Tumor Necrosis Factor biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 96
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16152630
- Full Text :
- https://doi.org/10.1002/jcb.20598