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An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice
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SYSNO ASEP 0543675 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice Author(s) Kimura, T. (JP)
Bosáková, Michaela (UZFG-Y) ORCID
Nonaka, Y. (JP)
Hrubá, Eva (UZFG-Y) ORCID
Yasuda, K. (JP)
Futakawa, S. (JP)
Kubota, T. (JP)
Fafílek, Bohumil (UZFG-Y) ORCID
Gregor, T. (CZ)
Abraham, S. P. (CZ)
Gomolková, Regina (UZFG-Y)
Belasková, S. (CZ)
Pešl, M. (CZ)
Csukasi, F. (US)
Duran, I. (US)
Fujiwara, M. (JP)
Kavková, M. (CZ)
Zikmund, T. (CZ)
Kaiser, J. (CZ)
Buchtová, Marcela (UZFG-Y) RID, ORCID
Krakow, D. (US)
Nakamura, Y. (JP)
Ozono, K. (JP)
Krejčí, Pavel (UZFG-Y) ORCIDArticle number eaba4226 Source Title Science Translational Medicine. - : American Association for the Advancement of Science - ISSN 1946-6234
Roč. 13, č. 592 (2021)Number of pages 14 s. Publication form Online - E Language eng - English Country US - United States Keywords achondroplasia ; FGFR3 ; bone growth Subject RIV EB - Genetics ; Molecular Biology OECD category Genetics and heredity (medical genetics to be 3) R&D Projects EF15_003/0000460 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UZFG-Y - RVO:67985904 UT WOS 000648584600002 EID SCOPUS 85105526279 DOI 10.1126/scitranslmed.aba4226 Annotation Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias. Workplace Institute of Animal Physiology and Genetics Contact Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Year of Publishing 2022 Electronic address https://stm.sciencemag.org/content/13/592/eaba4226
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