Atorvastatin stimulates the production of osteoprotegerin by human osteoblasts

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...

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Published in:Journal of cellular biochemistry 2005-12, Vol.96 (6), p.1244-1253
Main Authors: Viereck, Volker, Gründker, Carsten, Blaschke, Sabine, Frosch, Karl-Heinz, Schoppet, Michael, Emons, Günter, Hofbauer, Lorenz C.
Format: Article
Language:English
Subjects:
Adult
atorvastatin
Atorvastatin Calcium
Cell Differentiation - drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Female
Glucocorticoids - metabolism
Glucocorticoids - pharmacology
Glycoproteins - biosynthesis
Glycoproteins - drug effects
Glycoproteins - metabolism
Heptanoic Acids - metabolism
Heptanoic Acids - pharmacology
Humans
Male
mevalonate
Mevalonic Acid - metabolism
Models, Biological
osteoblast
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteoprotegerin
Pyrroles - metabolism
Pyrroles - pharmacology
RANK ligand
Receptors, Cytoplasmic and Nuclear - biosynthesis
Receptors, Cytoplasmic and Nuclear - drug effects
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Tumor Necrosis Factor - biosynthesis
Receptors, Tumor Necrosis Factor - drug effects
Receptors, Tumor Necrosis Factor - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - drug effects
RNA, Messenger - metabolism
Time Factors
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Summary: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‐κB 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 
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.20598