An RNA aptamer restores defective bone growth in FGFR3-related
skeletal dysplasia in mice

J 2021

An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice

KIMURA, T.; Michaela BOSÁKOVÁ; Y. NONAKA; Eva HRUBA; K. YASUDA et. al.

Základní údaje

Originální název

An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice

Autoři

Vydání

Science Translational Medicine, Washington, American Association for the Advancement of Science, 2021, 1946-6234

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 19.343

Kód RIV

RIV/00216224:14110/21:00119123

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1126/scitranslmed.aba4226

UT WoS

000648584600002

EID Scopus

2-s2.0-85105526279

Klíčová slova anglicky

RNA aptamer; defective bone growth; FGFR3-related skeletal dysplasia; mice

Štítky

14110115, 14110513, 14314010, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 2. 2022 10:06, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

GA17-09525S, projekt VaV

Název: Neobvyklé signální dráhy lidských receptorových tyrozinových kináz

Investor: Grantová agentura ČR, Neobvyklé signální dráhy lidských receptorových tyrozinových kináz

GA19-20123S, projekt VaV

Název: Regulace časného vývoje savčí končetiny pomocí nestabilních morfogenů z rodiny FGF (Akronym: Regulace časného vývoje savčí končetiny)

Investor: Grantová agentura ČR, Regulace časného vývoje savčí končetiny pomocí nestabilních morfogenů z rodiny FGF

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

MUNI/A/1325/2020, interní kód MU

Název: Biomedicínské vědy

Investor: Masarykova univerzita, Biomedicínské vědy

Citovat

KIMURA, T.; Michaela BOSÁKOVÁ; Y. NONAKA; Eva HRUBA; K. YASUDA; S. FUTAKAWA; T. KUBOTA; Bohumil FAFÍLEK; Tomáš GREGOR; Sara POOVAKULATHU ABRAHAM; Regína GOMOLKOVÁ; Silvie BELASKOVA; Martin PEŠL; F. CSUKASI; I. DURAN; M. FUJIWARA; Michaela KAVKOVA; Tomas ZIKMUND; Josef KAISER; Marcela BUCHTOVÁ; D. KRAKOW; Y. NAKAMURA; K. OZONO a Pavel KREJČÍ. An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice. Science Translational Medicine. Washington: American Association for the Advancement of Science, 2021, roč. 13, č. 592, s. "eaba4226", 14 s. ISSN 1946-6234. Dostupné z: https://doi.org/10.1126/scitranslmed.aba4226.

@article{1785579,
   author = {Kimura, T. and Bosáková, Michaela and Nonaka, Y. and Hruba, Eva and Yasuda, K. and Futakawa, S. and Kubota, T. and Fafílek, Bohumil and Gregor, Tomáš and Poovakulathu Abraham, Sara and Gomolková, Regína and Belaskova, Silvie and Pešl, Martin and Csukasi, F. and Duran, I. and Fujiwara, M. and Kavkova, Michaela and Zikmund, Tomas and Kaiser, Josef and Buchtová, Marcela and Krakow, D. and Nakamura, Y. and Ozono, K. and Krejčí, Pavel},
   article_location = {Washington},
   article_number = {592},
   doi = {https://doi.org/10.1126/scitranslmed.aba4226},
   keywords = {RNA aptamer; defective bone growth; FGFR3-related skeletal dysplasia; mice},
   language = {eng},
   issn = {1946-6234},
   journal = {Science Translational Medicine},
   title = {An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice},
   url = {https://stm.sciencemag.org/content/13/592/eaba4226},
   volume = {13},
   year = {2021}
}

TY  - JOUR
ID  - 1785579
AU  - Kimura, T. - Bosáková, Michaela - Nonaka, Y. - Hruba, Eva - Yasuda, K. - Futakawa, S. - Kubota, T. - Fafílek, Bohumil - Gregor, Tomáš - Poovakulathu Abraham, Sara - Gomolková, Regína - Belaskova, Silvie - Pešl, Martin - Csukasi, F. - Duran, I. - Fujiwara, M. - Kavkova, Michaela - Zikmund, Tomas - Kaiser, Josef - Buchtová, Marcela - Krakow, D. - Nakamura, Y. - Ozono, K. - Krejčí, Pavel
PY  - 2021
TI  - An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice
JF  - Science Translational Medicine
VL  - 13
IS  - 592
SP  - "eaba4226"
EP  - "eaba4226"
PB  - American Association for the Advancement of Science
SN  - 19466234
KW  - RNA aptamer
KW  - defective bone growth
KW  - FGFR3-related skeletal dysplasia
KW  - mice
UR  - https://stm.sciencemag.org/content/13/592/eaba4226
N2  - 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.
ER  -

KIMURA, T.; Michaela BOSÁKOVÁ; Y. NONAKA; Eva HRUBA; K. YASUDA; S. FUTAKAWA; T. KUBOTA; Bohumil FAFÍLEK; Tomáš GREGOR; Sara POOVAKULATHU ABRAHAM; Regína GOMOLKOVÁ; Silvie BELASKOVA; Martin PEŠL; F. CSUKASI; I. DURAN; M. FUJIWARA; Michaela KAVKOVA; Tomas ZIKMUND; Josef KAISER; Marcela BUCHTOVÁ; D. KRAKOW; Y. NAKAMURA; K. OZONO a Pavel KREJČÍ. An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice. \textit{Science Translational Medicine}. Washington: American Association for the Advancement of Science, 2021, roč.~13, č.~592, s.~''eaba4226'', 14 s. ISSN~1946-6234. Dostupné z: https://doi.org/10.1126/scitranslmed.aba4226.

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