Polycystin-1 modulates RUNX2 activation and osteocalcin gene expression via ERK signalling in a human craniosynostosis cell model.
ERK
PC1
RUNX2
craniosynostosis
dolichocephaly
mechanosensation
mechanotransduction
osteoblast differentiation
osteocalcin
trigonocephaly
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
06
02
2021
received:
21
01
2021
accepted:
09
02
2021
pubmed:
4
3
2021
medline:
18
9
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
Craniosynostosis refers to the premature fusion of one or more cranial sutures leading to skull shape deformities and brain growth restriction. Among the many factors that contribute to abnormal suture fusion, mechanical forces seem to play a major role. Nevertheless, the underlying mechanobiology-related mechanisms of craniosynostosis still remain unknown. Understanding how aberrant mechanosensation and mechanotransduction drive premature suture fusion will offer important insights into the pathophysiology of craniosynostosis and result in the development of new therapies, which can be used to intervene at an early stage and prevent premature suture fusion. Herein, we provide evidence for the first time on the role of polycystin-1 (PC1), a key protein in cellular mechanosensitivity, in craniosynostosis, using primary cranial suture cells isolated from patients with trigonocephaly and dolichocephaly, two common types of craniosynostosis. Initially, we showed that PC1 is expressed at the mRNA and protein level in both trigonocephaly and dolichocephaly cranial suture cells. Followingly, by utilizing an antibody against the mechanosensing extracellular N-terminal domain of PC1, we demonstrated that PC1 regulates runt-related transcription factor 2 (RUNX2) activation and osteocalcin gene expression via extracellular signal-regulated kinase (ERK) signalling in our human craniosynostosis cell model. Altogether, our study reveals a novel mechanotransduction signalling axis, PC1-ERK-RUNX2, which affects osteoblastic differentiation in cranial suture cells from trigonocephaly and dolichocephaly patients.
Identifiants
pubmed: 33656806
doi: 10.1111/jcmm.16391
pmc: PMC8034462
doi:
Substances chimiques
Core Binding Factor Alpha 1 Subunit
0
RUNX2 protein, human
0
TRPP Cation Channels
0
polycystic kidney disease 1 protein
0
Osteocalcin
104982-03-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3216-3225Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK090868
Pays : United States
Informations de copyright
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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