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Statins do not inhibit the FGFR signaling in chondrocytes
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SYSNO ASEP 0480628 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Statins do not inhibit the FGFR signaling in chondrocytes Tvůrce(i) Fafílek, B. (CZ)
Hampl, Marek (UZFG-Y) ORCID
Říčánková, N. (CZ)
Veselá, Iva (UZFG-Y)
Bálek, L. (CZ)
Kunová Bosáková, M. (CZ)
Gudernová, I. (CZ)
Vařecha, M. (CZ)
Buchtová, Marcela (UZFG-Y) RID, ORCID
Krejčí, P. (CZ)Zdroj.dok. Osteoarthritis and Cartilage. - : Elsevier - ISSN 1063-4584
Roč. 25, č. 9 (2017), s. 1522-1530Poč.str. 9 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova statins ; FGF signaling ; chondrocytes Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Developmental biology CEP GA14-31540S GA ČR - Grantová agentura ČR Institucionální podpora UZFG-Y - RVO:67985904 UT WOS 000407934000019 EID SCOPUS 85020752812 DOI 10.1016/j.joca.2017.05.014 Anotace 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.Pracoviště Ústav živočišné fyziologie a genetiky Kontakt Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Rok sběru 2018
Počet záznamů: 1