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Simvastatin induces osteogenic differentiation of murine embryonic stem cells
Journal of bone and mineral research, 2010-11, Vol.25 (11), p.2470-2478
Pagkalos, Joseph
Cha, Jae Min
Kang, Yunyi
Heliotis, Manolis
Tsiridis, Eleftherios
Mantalaris, Athanasios
2010
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Pagkalos, Joseph
Cha, Jae Min
Kang, Yunyi
Heliotis, Manolis
Tsiridis, Eleftherios
Mantalaris, Athanasios
Titel
Simvastatin induces osteogenic differentiation of murine embryonic stem cells
Ist Teil von
Journal of bone and mineral research, 2010-11, Vol.25 (11), p.2470-2478
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2010
Quelle
Wiley Online Library - AutoHoldings Journals
Beschreibungen/Notizen
Statins are potent inhibitors of cholesterol synthesis. Several statins are available with different molecular and pharmacokinetic properties. Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin, allowing its passive diffusion through the cell membrane. In vitro studies on bone marrow stromal cells, osteoblast‐like cells, and embryonic stem cells have shown statins to have cholesterol‐independent anabolic effects on bone metabolism; alas, statins were supplemented in osteogenic medium, which does not facilitate elucidation of their potential osteoinductive properties. Embryonic stem cells (ESCs), derived from the inner cell mass of the blastocyst, are unique in that they enjoy perpetual self‐proliferation, are pluripotent, and are able to differentiate toward all the cellular lineages composing the body, including the osteogenic lineage. Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases, even though there are several hurdles that still need to be overcome. Herein we demonstrate, for the first time to our knowledge, that simvastatin induces murine ESC (mESC) differentiation toward the osteogenic lineage in the absence of osteoinductive supplements. Specifically, we found that a simvastatin concentration in the micromolar range and higher was toxic to the cells and that an effective concentration for osteoinduction is 0.1 nM, as shown by increased alizarin red staining as well as increased osteocalcin and osetrix gene expression. These results suggest that in the future, lipophilic simvastatin may provide a novel pharmacologic agent for bone tissue engineering applications. © 2010 American Society for Bone and Mineral Research.
Sprache
Englisch
Identifikatoren
ISSN: 0884-0431
eISSN: 1523-4681
DOI: 10.1002/jbmr.163
Titel-ID: cdi_proquest_miscellaneous_1891869088
Format
–
Schlagworte
Alkaline Phosphatase - metabolism
,
Animals
,
Anthraquinones
,
Biological and medical sciences
,
Bone Morphogenetic Protein 2 - metabolism
,
Cell Differentiation - drug effects
,
Embryonic Stem Cells - cytology
,
Embryonic Stem Cells - drug effects
,
Embryonic Stem Cells - enzymology
,
Fundamental and applied biological sciences. Psychology
,
Hep G2 Cells
,
Humans
,
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
,
Mice
,
murine embryonic stem cells
,
Osteogenesis - drug effects
,
osteoinduction
,
Polymerase Chain Reaction
,
simvastatin
,
Simvastatin - pharmacology
,
Skeleton and joints
,
Vertebrates: osteoarticular system, musculoskeletal system
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