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.

Basic information

Original name

Statins do not inhibit the FGFR signaling in chondrocytes

Authors

FAFÍLEK, Bohumil (203 Czech Republic, belonging to the institution), Marek HAMPL (203 Czech Republic, belonging to the institution), Nikola ŘIČÁNKOVÁ (203 Czech Republic, belonging to the institution), I. VESELA (203 Czech Republic), Lukáš BÁLEK (203 Czech Republic, belonging to the institution), Michaela BOSÁKOVÁ (203 Czech Republic, belonging to the institution), Iva GUDERNOVÁ (203 Czech Republic, belonging to the institution), Miroslav VAŘECHA (203 Czech Republic, belonging to the institution), marcela BUCHTOVÁ (203 Czech Republic, belonging to the institution) and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30211 Orthopaedics

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.454

RIV identification code

RIV/00216224:14110/17:00097411

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000407934000019

Keywords in English

Achondroplasia; Chondrocytes; FGF signaling; Statins

Abstract

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.

Links

LH12004, research and development project

Name: FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci (Acronym: AMVIS-FGFR3)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/0810/2016, interní kód MU

Name: Molekulární a buněčná biologie

Investor: Masaryk University, Category A

Citovat

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. 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.

@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.

Detailed Information on Publication Record