Pharmacological intervention of the FGF-PTH axis as a potential
therapeutic for craniofacial ciliopathies

J 2022

Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies

PAESE, Christian Louis Bonatto, Ching-Fang CHANG, Daniela KRISTEKOVÁ a Samantha A. BRUGMANN

Základní údaje

Originální název

Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies

Autoři

PAESE, Christian Louis Bonatto, Ching-Fang CHANG, Daniela KRISTEKOVÁ (703 Slovensko, domácí) a Samantha A. BRUGMANN (garant)

Vydání

DMM Disease Models and Mechanisms, Company of Biologists Ltd, 2022, 1754-8403

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.300

Kód RIV

RIV/00216224:14310/22:00128055

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1242/dmm.049611

UT WoS

000864078600001

Klíčová slova anglicky

Primary cilia; Ciliopathies; FGF; C2CD3; Micrognathia; talpid(2)

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 1. 2023 15:52, Mgr. Marie Šípková, DiS.

Anotace

V originále

Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with both kidney and skeletal anomalies (orofaciodigital syndrome 14), we identified disruptions in the FGF23–PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. Although pharmacological intervention with the U.S. Food and Drug Administration (FDA)-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target SPRY2, it did not significantly rescue micrognathia. In contrast, treatment with a cocktail of AZD4547 and teriparatide acetate, a PTH agonist and FDA-approved treatment for osteoporosis, resulted in molecular, cellular and phenotypic rescue of ciliopathic micrognathia in talpid2 mutants. Together, these data provide novel insight into pathological molecular mechanisms associated with ciliopathic skeletal phenotypes and a potential therapeutic strategy for a pleiotropic disease class with limited to no treatment options.

Citovat

PAESE, Christian Louis Bonatto, Ching-Fang CHANG, Daniela KRISTEKOVÁ a Samantha A. BRUGMANN. Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies. DMM Disease Models and Mechanisms. Company of Biologists Ltd, 2022, roč. 15, č. 8, s. 1-10. ISSN 1754-8403. Dostupné z: https://dx.doi.org/10.1242/dmm.049611.

@article{2247393,
   author = {Paese, Christian Louis Bonatto and Chang, ChingandFang and Kristeková, Daniela and Brugmann, Samantha A.},
   article_number = {8},
   doi = {http://dx.doi.org/10.1242/dmm.049611},
   keywords = {Primary cilia; Ciliopathies; FGF; C2CD3; Micrognathia; talpid(2)},
   language = {eng},
   issn = {1754-8403},
   journal = {DMM Disease Models and Mechanisms},
   title = {Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies},
   url = {https://doi.org/10.1242/dmm.049611},
   volume = {15},
   year = {2022}
}

TY  - JOUR
ID  - 2247393
AU  - Paese, Christian Louis Bonatto - Chang, Ching-Fang - Kristeková, Daniela - Brugmann, Samantha A.
PY  - 2022
TI  - Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies
JF  - DMM Disease Models and Mechanisms
VL  - 15
IS  - 8
SP  - 1-10
EP  - 1-10
PB  - Company of Biologists Ltd
SN  - 17548403
KW  - Primary cilia
KW  - Ciliopathies
KW  - FGF
KW  - C2CD3
KW  - Micrognathia
KW  - talpid(2)
UR  - https://doi.org/10.1242/dmm.049611
N2  - Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with both kidney and skeletal anomalies (orofaciodigital syndrome 14), we identified disruptions in the FGF23–PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. Although pharmacological intervention with the U.S. Food and Drug Administration (FDA)-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target SPRY2, it did not significantly rescue micrognathia. In contrast, treatment with a cocktail of AZD4547 and teriparatide acetate, a PTH agonist and FDA-approved treatment for osteoporosis, resulted in molecular, cellular and phenotypic rescue of ciliopathic micrognathia in talpid2 mutants. Together, these data provide novel insight into pathological molecular mechanisms associated with ciliopathic skeletal phenotypes and a potential therapeutic strategy for a pleiotropic disease class with limited to no treatment options.
ER  -

PAESE, Christian Louis Bonatto, Ching-Fang CHANG, Daniela KRISTEKOVÁ a Samantha A. BRUGMANN. Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies. \textit{DMM Disease Models and Mechanisms}. Company of Biologists Ltd, 2022, roč.~15, č.~8, s.~1-10. ISSN~1754-8403. Dostupné z: https://dx.doi.org/10.1242/dmm.049611.

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