Other formats:
BibTeX
LaTeX
RIS
@article{1399055,
author = {Bálek, Lukáš and Gudernová, Iva and Vesela, Iva and Hampl, Marek and Oralová, Veronika and Bosáková, Michaela and Vařecha, Miroslav and Němec, Pavel and Hall, Terence and Abbadessa, Giovanni and Hatch, Nan and Buchtová, marcela and Krejčí, Pavel},
article_location = {NEW YORK},
article_number = {DEC 2017},
doi = {http://dx.doi.org/10.1016/j.bone.2017.08.016},
keywords = {ARQ 087; Fibroblast growth factor receptor; FGFR; Skeletal dysplasia; Achondroplasia; Craniosynostosis; Inhibitor},
language = {eng},
issn = {8756-3282},
journal = {Bone},
title = {ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3},
volume = {105},
year = {2017}
}
TY - JOUR
ID - 1399055
AU - Bálek, Lukáš - Gudernová, Iva - Vesela, Iva - Hampl, Marek - Oralová, Veronika - Bosáková, Michaela - Vařecha, Miroslav - Němec, Pavel - Hall, Terence - Abbadessa, Giovanni - Hatch, Nan - Buchtová, marcela - Krejčí, Pavel
PY - 2017
TI - ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3
JF - Bone
VL - 105
IS - DEC 2017
SP - 57-66
EP - 57-66
PB - Elsevier
SN - 87563282
KW - ARQ 087
KW - Fibroblast growth factor receptor
KW - FGFR
KW - Skeletal dysplasia
KW - Achondroplasia
KW - Craniosynostosis
KW - Inhibitor
N2 - Tyrosine kinase inhibitors are being developed for therapy of malignancies caused by oncogenic FGFR signaling but little is known about their effect in congenital chondrodysplasias or craniosynostoses that associate with activating FGFR mutations. Here, we investigated the effects of novel FGFR inhibitor, ARQ 087, in experimental models of aberrant FGFR3 signaling in cartilage. In cultured chondrocytes, ARQ 087 efficiently rescued all major effects of pathological FGFR3 activation, i.e. inhibition of chondrocyte proliferation, loss of extracellular matrix and induction of premature senescence. In ex vivo tibia organ cultures, ARQ087 restored normal growth plate architecture and eliminated the suppressing FGFR3 effect on chondrocyte hypertrophic differentiation, suggesting that it targets the FGFR3 pathway specifically, i.e. without interference with other pro-growth pathways. Moreover, ARQ 087 inhibited activity of FGFR1 and FGFR2 mutants associated with Pfeiffer, Apert and Beare-Stevenson craniosynostoses, and rescued FGFR-driven excessive osteogenic differentiation in mouse mesenchymal micromass cultures or in ex vivo calvarial organ cultures. Our data warrant further development of ARQ 087 for clinical use in skeletal disorders caused by activating FGFR mutations. (C) 2017 Elsevier Inc. All rights reserved.
ER -
BÁLEK, Lukáš, Iva GUDERNOVÁ, Iva VESELA, Marek HAMPL, Veronika ORALOVÁ, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Pavel NĚMEC, Terence HALL, Giovanni ABBADESSA, Nan HATCH, marcela BUCHTOVÁ and Pavel KREJČÍ. ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3. \textit{Bone}. NEW YORK: Elsevier, 2017, vol.~105, DEC 2017, p.~57-66. ISSN~8756-3282. Available from: https://dx.doi.org/10.1016/j.bone.2017.08.016.
|
