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@article{1388208,
author = {Fafílek, Bohumil and Hampl, Marek and Řičánková, Nikola and Vesela, I. and Bálek, Lukáš and Bosáková, Michaela and Gudernová, Iva and Vařecha, Miroslav and Buchtová, marcela and Krejčí, Pavel},
article_location = {Oxford},
article_number = {9},
doi = {http://dx.doi.org/10.1016/j.joca.2017.05.014},
keywords = {Achondroplasia; Chondrocytes; FGF signaling; Statins},
language = {eng},
issn = {1063-4584},
journal = {Osteoarthritis and Cartilage},
title = {Statins do not inhibit the FGFR signaling in chondrocytes},
volume = {25},
year = {2017}
}
TY - JOUR
ID - 1388208
AU - Fafílek, Bohumil - Hampl, Marek - Řičánková, Nikola - Vesela, I. - Bálek, Lukáš - Bosáková, Michaela - Gudernová, Iva - Vařecha, Miroslav - Buchtová, marcela - Krejčí, Pavel
PY - 2017
TI - Statins do not inhibit the FGFR signaling in chondrocytes
JF - Osteoarthritis and Cartilage
VL - 25
IS - 9
SP - 1522-1530
EP - 1522-1530
PB - Elsevier Science Inc.
SN - 10634584
KW - Achondroplasia
KW - Chondrocytes
KW - FGF signaling
KW - Statins
N2 - 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.
ER -
FAFÍLEK, Bohumil, Marek HAMPL, Nikola ŘIČÁNKOVÁ, I. VESELA, Lukáš BÁLEK, Michaela BOSÁKOVÁ, Iva GUDERNOVÁ, Miroslav VAŘECHA, marcela BUCHTOVÁ and Pavel KREJČÍ. Statins do not inhibit the FGFR signaling in chondrocytes. \textit{Osteoarthritis and Cartilage}. Oxford: Elsevier Science Inc., 2017, vol.~25, No~9, p.~1522-1530. ISSN~1063-4584. Available from: https://dx.doi.org/10.1016/j.joca.2017.05.014.
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