Publication detail

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

Kimura, T. Bosakova, M. Nonaka, Y. Hruba, E. Yasuda, K. Futakawa, S. Kubota, T. Fafilek, B. Gregor, T. Abraham, S.P. Gomolkova, R Belaskova, S., Pesl M.b, c, f,Csukasi F.g, h,Duran I.g, h,Fujiwara, M. Kavkova, M. Zikmund, T. Kaiser, J. Buchtova, M. Krakow, D. Nakamura, Y. Ozono, K. Krejci, P.

Original Title

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

Type

journal article in Web of Science

Language

English

Original Abstract

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.

Keywords

NATRIURETIC-PEPTIDE RESISTANCE; FACTOR RECEPTOR-3; CHONDROCYTE PROLIFERATION; TALL STATURE; FGFR3; ACHONDROPLASIA; MUTATION; RESCUES; HYPOCHONDROPLASIA; PREVALENCE

Authors

Kimura, T.; Bosakova, M.; Nonaka, Y.; Hruba, E.; Yasuda, K.; Futakawa, S.; Kubota, T.; Fafilek, B.; Gregor, T.; Abraham, S.P.; Gomolkova, R; Belaskova, S., Pesl M.b, c, f,Csukasi F.g, h,Duran I.g, h,Fujiwara, M.; Kavkova, M.; Zikmund, T.; Kaiser, J.; Buchtova, M.; Krakow, D.; Nakamura, Y.; Ozono, K.; Krejci, P.

Released

5. 5. 2021

Publisher

AMER ASSOC ADVANCEMENT SCIENCE

Location

WASHINGTON

ISBN

1946-6242

Periodical

Science Translational Medicine

Year of study

13

Number

592

State

United States of America

Pages from

eaba4226-1

Pages to

eaba422-14

Pages count

14

URL