Statins do not inhibit the FGFR signaling in chondrocytes

J 2017

Statins do not inhibit the FGFR signaling in chondrocytes

FAFÍLEK, Bohumil, Marek HAMPL, Nikola ŘIČÁNKOVÁ, I. VESELA, Lukáš BÁLEK et. al.

Základní údaje

Originální název

Statins do not inhibit the FGFR signaling in chondrocytes

Autoři

FAFÍLEK, Bohumil (203 Česká republika, domácí), Marek HAMPL (203 Česká republika, domácí), Nikola ŘIČÁNKOVÁ (203 Česká republika, domácí), I. VESELA (203 Česká republika), Lukáš BÁLEK (203 Česká republika, domácí), Michaela BOSÁKOVÁ (203 Česká republika, domácí), Iva GUDERNOVÁ (203 Česká republika, domácí), Miroslav VAŘECHA (203 Česká republika, domácí), marcela BUCHTOVÁ (203 Česká republika, domácí) a Pavel KREJČÍ (203 Česká republika, garant, domácí)

Vydání

Osteoarthritis and Cartilage, Oxford, Elsevier Science Inc. 2017, 1063-4584

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30211 Orthopaedics

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.454

Kód RIV

RIV/00216224:14110/17:00097411

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/j.joca.2017.05.014

UT WoS

000407934000019

Klíčová slova anglicky

Achondroplasia; Chondrocytes; FGF signaling; Statins

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2018 19:26, Soňa Böhmová

Anotace

V originále

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.

Návaznosti

LH12004, projekt VaV

Název: FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci (Akronym: AMVIS-FGFR3)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci

MUNI/A/0810/2016, interní kód MU

Název: Molekulární a buněčná biologie

Investor: Masarykova univerzita, Molekulární a buněčná biologie, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

FAFÍLEK, Bohumil, Marek HAMPL, Nikola ŘIČÁNKOVÁ, I. VESELA, Lukáš BÁLEK, Michaela BOSÁKOVÁ, Iva GUDERNOVÁ, Miroslav VAŘECHA, marcela BUCHTOVÁ a Pavel KREJČÍ. Statins do not inhibit the FGFR signaling in chondrocytes. Osteoarthritis and Cartilage. Oxford: Elsevier Science Inc., 2017, roč. 25, č. 9, s. 1522-1530. ISSN 1063-4584. Dostupné z: https://dx.doi.org/10.1016/j.joca.2017.05.014.

@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 a Pavel KREJČÍ. Statins do not inhibit the FGFR signaling in chondrocytes. \textit{Osteoarthritis and Cartilage}. Oxford: Elsevier Science Inc., 2017, roč.~25, č.~9, s.~1522-1530. ISSN~1063-4584. Dostupné z: https://dx.doi.org/10.1016/j.joca.2017.05.014.

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