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.

Basic information

Original name

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

Authors

KIMURA, T., Michaela BOSÁKOVÁ (203 Czech Republic, belonging to the institution), Y. NONAKA, Eva HRUBA (203 Czech Republic), K. YASUDA, S. FUTAKAWA, T. KUBOTA, Bohumil FAFÍLEK (203 Czech Republic, belonging to the institution), Tomáš GREGOR (203 Czech Republic, belonging to the institution), Sara POOVAKULATHU ABRAHAM (356 India, belonging to the institution), Regína GOMOLKOVÁ (203 Czech Republic, belonging to the institution), Silvie BELASKOVA (203 Czech Republic), Martin PEŠL (203 Czech Republic, belonging to the institution), F. CSUKASI, I. DURAN, M. FUJIWARA, Michaela KAVKOVA (203 Czech Republic), Tomas ZIKMUND (203 Czech Republic), Josef KAISER (203 Czech Republic), Marcela BUCHTOVÁ (203 Czech Republic, belonging to the institution), D. KRAKOW, Y. NAKAMURA, K. OZONO and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 19.319

RIV identification code

RIV/00216224:14110/21:00119123

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1126/scitranslmed.aba4226

UT WoS

000648584600002

Keywords in English

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

Abstract

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.

Links

GA17-09525S, research and development project

Name: Neobvyklé signální dráhy lidských receptorových tyrozinových kináz

Investor: Czech Science Foundation

GA19-20123S, research and development project

Name: Regulace časného vývoje savčí končetiny pomocí nestabilních morfogenů z rodiny FGF (Acronym: Regulace časného vývoje savčí končetiny)

Investor: Czech Science Foundation

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

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

MUNI/A/1325/2020, interní kód MU

Name: Biomedicínské vědy

Investor: Masaryk University

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 and 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, vol. 13, No 592, p. "eaba4226", 14 pp. ISSN 1946-6234. Available from: https://dx.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 = {http://dx.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 and 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, vol.~13, No~592, p.~''eaba4226'', 14 pp. ISSN~1946-6234. Available from: https://dx.doi.org/10.1126/scitranslmed.aba4226.

Detailed Information on Publication Record