Počet záznamů: 1
Statins do not inhibit the FGFR signaling in chondrocytes
- 1.0480628 - UZFG-Y 2018 RIV GB eng J - Článek v odborném periodiku
Fafílek, B. - Hampl, Marek - Říčánková, N. - Veselá, Iva - Bálek, L. - Kunová Bosáková, M. - Gudernová, I. - Vařecha, M. - Buchtová, Marcela - Krejčí, P.
Statins do not inhibit the FGFR signaling in chondrocytes.
Osteoarthritis and Cartilage. Roč. 25, č. 9 (2017), s. 1522-1530. ISSN 1063-4584
Grant CEP: GA ČR(CZ) GA14-31540S
Grant ostatní:GA MŠk(CZ) LH12004
Institucionální podpora: RVO:67985904
Klíčová slova: statins * FGF signaling * chondrocytes
Kód oboru RIV: EB - Genetika a molekulární biologie
Obor OECD: Developmental biology
Impakt faktor: 5.454, rok: 2017
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.
Trvalý link: http://hdl.handle.net/11104/0276360