Statins do not inhibit the FGFR signaling in chondrocytes
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
28583899
DOI
10.1016/j.joca.2017.05.014
PII: S1063-4584(17)31024-5
Knihovny.cz E-resources
- Keywords
- Achondroplasia, Chondrocytes, FGF signaling, Statins,
- MeSH
- Cell Differentiation drug effects MeSH
- Cell Line MeSH
- Chondrocytes drug effects metabolism MeSH
- Chondrogenesis drug effects MeSH
- Limb Buds drug effects metabolism MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mice MeSH
- Receptor, Fibroblast Growth Factor, Type 3 antagonists & inhibitors metabolism MeSH
- Signal Transduction drug effects MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology MeSH
- Tissue Culture Techniques MeSH
- Tibia drug effects embryology growth & development MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Receptor, Fibroblast Growth Factor, Type 3 MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH
OBJECTIVE: Statins are widely used drugs for cholesterol lowering, which were recently found to counteract the effects of aberrant fibroblast growth factor receptor (FGFR3) signaling in cell and animal models of FGFR3-related chondrodysplasia. This opened an intriguing therapeutic possibility for human dwarfing conditions caused by gain-of-function mutations in FGFR3, although the mechanism of statin action on FGFR3 remains unclear. Here, we determine the effect of statins on FGFR signaling in chondrocytes. DESIGN: Cultured chondrocyte cell lines, mouse embryonic tibia cultures and limb bud micromasses were treated with FGF2 to activate FGFR signaling. The effects of atorvastatin, fluvastatin, lovastatin and pravastatin on FGFR3 protein stability and on FGFR-mediated chondrocyte growth-arrest, loss of extracellular matrix (ECM), induction of premature senescence and hypertrophic differentiation were evaluated. RESULTS: Statins did not alter the level of FGFR3 protein expression nor produce any effect on FGFR-mediated inhibition of chondrocyte proliferation and hypertrophic differentiation in cultured chondrocyte cell lines, mouse tibia cultures or limb bud micromasses. CONCLUSION: We conclude that statins do not inhibit the FGFR signaling in chondrocytes. Therefore the statin-mediated rescue of FGFR3-related chondrodysplasia, described before, is likely not intrinsic to the growth plate cartilage.
Department of Biology Faculty of Medicine Masaryk University 62500 Brno Czech Republic
Institute of Animal Physiology and Genetics AS CR 60200 Brno Czech Republic
References provided by Crossref.org
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