FGFR2 Mutation p.Cys342Arg Enhances Mitochondrial Metabolism-Mediated Osteogenesis via FGF/FGFR-AMPK-Erk1/2 Axis in Crouzon Syndrome.

ABSTRACT:

Background

Crouzon syndrome ([OMIM] #123500) caused by FGFR2 mutation is an autosomal dominant syndrome with craniosynostosis, the underlying mechanism of which remains obscure.

Methods

First, whole exome sequencing was used to screen the possible pathogenic variant in two sporadic patients with Crouzon syndrome. The investigation of primary and secondary structures as well as the conservation analysis of FGFR2 mutation (p.Cys342Arg) was performed. Then, wild-type and mutant overexpression plasmids were constructed and transfected into pre-osteoblastic murine cell line MC3T3-E1 cells. Osteogenesis and mitochondrial metabolism were analyzed by CCK8, ALP staining and ALP activity, alizarin red staining, qRT-PCR, Western blot, seahorse assays and mitochondrial staining. The siR

SUBMITTER: Wang Y 

PROVIDER: S-EPMC9563077 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature