TY - JOUR
TI - Polycystin-1 modulates RUNX2 activation and osteocalcin gene expression via ERK signalling in a human craniosynostosis cell model
AU - Katsianou, M.
AU - Papavassiliou, K.A.
AU - Zoi, I.
AU - Gargalionis, A.N.
AU - Panagopoulos, D.
AU - Themistocleous, M.S.
AU - Piperi, C.
AU - Papavassiliou, A.G.
AU - Basdra, E.K.
JO - Journal of Cellular and Molecular Medicine
PY - 2021
VL - 25
TODO - 7
SP - 3216-3225
PB - John Wiley and Sons Inc
SN - 1582-1838, 1582-4934
TODO - 10.1111/jcmm.16391
TODO - mitogen activated protein kinase;  osteocalcin;  polycystin 1;  transcription factor RUNX2, Apgar score;  Article;  birth weight;  bone development;  cell differentiation;  child;  clinical article;  controlled study;  cranial suture;  craniofacial synostosis;  densitometry;  dolichocephaly;  female;  gene expression;  human;  human cell;  human tissue;  in vitro study;  male;  MAPK signaling;  mechanoreceptor;  mechanotransduction;  periodontal ligament;  prematurity;  protein expression;  protein phosphorylation;  real time polymerase chain reaction;  RNA isolation;  trigonocephaly;  Western blotting
TODO - 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. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
ER -