Statins do not inhibit the FGFR signaling in chondrocytes
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
28583899
DOI
10.1016/j.joca.2017.05.014
PII: S1063-4584(17)31024-5
Knihovny.cz E-zdroje
- Klíčová slova
- Achondroplasia, Chondrocytes, FGF signaling, Statins,
- MeSH
- buněčná diferenciace účinky léků MeSH
- buněčné linie MeSH
- chondrocyty účinky léků metabolismus MeSH
- chondrogeneze účinky léků MeSH
- končetinové pupeny účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- lidé MeSH
- myši MeSH
- receptor fibroblastových růstových faktorů, typ 3 antagonisté a inhibitory metabolismus MeSH
- signální transdukce účinky léků MeSH
- statiny farmakologie MeSH
- techniky tkáňových kultur MeSH
- tibie účinky léků embryologie růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- receptor fibroblastových růstových faktorů, typ 3 MeSH
- statiny 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
Citace poskytuje Crossref.org
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