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Citations to this article

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model
Davide Komla-Ebri, … , Martin Biosse-Duplan, Laurence Legeai-Mallet
Davide Komla-Ebri, … , Martin Biosse-Duplan, Laurence Legeai-Mallet
Published April 11, 2016
Citation Information: J Clin Invest. 2016;126(5):1871-1884. https://doi.org/10.1172/JCI83926.
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Research Article Bone biology Article has an altmetric score of 376

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

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Abstract

Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3–encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3Y367C/+ mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3Y367C/+ mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3Y367C/+ mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH.

Authors

Davide Komla-Ebri, Emilie Dambroise, Ina Kramer, Catherine Benoist-Lasselin, Nabil Kaci, Cindy Le Gall, Ludovic Martin, Patricia Busca, Florent Barbault, Diana Graus-Porta, Arnold Munnich, Michaela Kneissel, Federico Di Rocco, Martin Biosse-Duplan, Laurence Legeai-Mallet

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 Total
Citations: 3 3 10 9 6 8 3 2 6 2 52
Citation information
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Citations to this article in year 2022 (9)

Title and authors Publication Year
Disease-specific complications and multidisciplinary interventions in achondroplasia
H Kitoh, M Matsushita, K Mishima, Y Kamiya, K Sawamura
Journal of Bone and Mineral Metabolism 2022
Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia
L Martin, N Kaci, C Benoist-Lasselin, M Mondoloni, S Decaudaveine, V Estibals, M Cornille, L Loisay, J Flipo, B Demuynck, M de la Luz Cádiz-Gurrea, F Barbault, S Fernández-Arroyo, L Schibler, A Segura-Carretero, E Dambroise, L Legeai-Mallet
Bone Research 2022
Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish
G Takemoto, M Matsushita, T Okamoto, T Ito, Y Matsuura, C Takashima, T Chen-Yoshikawa, H Ebi, S Imagama, H Kitoh, K Ohno, Y Hosono
Frontiers in Cell and Developmental Biology 2022
FGFR3 overactivation in the brain is responsible for memory impairments in Crouzon syndrome mouse model.
Cornille M, Moriceau S, Khonsari RH, Heuzé Y, Loisay L, Boitez V, Morice A, Arnaud E, Collet C, Bensidhoum M, Kaci N, Boddaert N, Paternoster G, Rauschendorfer T, Werner S, Mansour SL, Di Rocco F, Oury F, Legeai-Mallet L
2022
Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies.
Savarirayan R, De Bergua JM, Arundel P, McDevitt H, Cormier-Daire V, Saraff V, Skae M, Delgado B, Leiva-Gea A, Santos-Simarro F, Salles JP, Nicolino M, Rossi M, Kannu P, Bober MB, Phillips J 3rd, Saal H, Harmatz P, Burren C, Gotway G, Cho T, Muslimova E, Weng R, Rogoff D, Hoover-Fong J, Irving M
Therapeutic Advances in Musculoskeletal Diseases 2022
Glutathione-Mediated Conjugation of Anticancer Drugs: An Overview of Reaction Mechanisms and Biological Significance for Drug Detoxification and Bioactivation
Potęga A
Molecules (Basel, Switzerland) 2022
The novel FGFR inhibitor F1-7 induces DNA damage and cell death in colon cells
Liu Y, Zhang L, Chen X, Chen D, Shi X, Song J, Wu J, Huang F, Xia Q, Xiang Y, Zheng X, Cai Y
British Journal of Cancer 2022
Meclozine ameliorates bone mineralization and growth plate structure in a mouse model of X‑linked hypophosphatemia
Kamiya Y, Matsushita M, Mishima K, Ohkawara B, Michigami T, Imagama S, Ohno K, Kitoh H
Experimental and therapeutic medicine 2022
New developments in the biology of fibroblast growth factors
Ornitz DM, Itoh N
2022

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