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Nevertheless, the underlying mechanobiology\u2010related 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\u20101 (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\u2010terminal domain of PC1, we demonstrated that PC1 regulates runt\u2010related transcription factor 2 (RUNX2) activation and <jats:italic>osteocalcin<\/jats:italic> gene expression via extracellular signal\u2013regulated kinase (ERK) signalling in our human craniosynostosis cell model. Altogether, our study reveals a novel mechanotransduction signalling axis, PC1\u2010ERK\u2010RUNX2, which affects osteoblastic differentiation in cranial suture cells from trigonocephaly and dolichocephaly patients.<\/jats:p>","DOI":"10.1111\/jcmm.16391","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T13:41:00Z","timestamp":1614778860000},"page":"3216-3225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Polycystin\u20101 modulates RUNX2 activation and <i>osteocalcin<\/i> gene expression via ERK signalling in a human craniosynostosis cell model"],"prefix":"10.1111","volume":"25","author":[{"given":"Maira","family":"Katsianou","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-745X","authenticated-orcid":false,"given":"Kostas A.","family":"Papavassiliou","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilianna","family":"Zoi","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios N.","family":"Gargalionis","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Panagopoulos","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Agia Sofia\u2019 Children's Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios S.","family":"Themistocleous","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Agia Sofia\u2019 Children's Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2701-0618","authenticated-orcid":false,"given":"Christina","family":"Piperi","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5803-4527","authenticated-orcid":false,"given":"Athanasios G.","family":"Papavassiliou","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0913-9354","authenticated-orcid":false,"given":"Efthimia K.","family":"Basdra","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Medical School National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2014.07.004"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbacli.2016.04.006"},{"issue":"4","key":"e_1_2_10_4_1","first-page":"e421","article-title":"Non\u2010syndromic craniosynostosis in children: Scoping review","volume":"23","author":"Garrocho\u2010Rangel A","year":"2018","journal-title":"Med Oral Patol Oral Cir Bucal"},{"issue":"2","key":"e_1_2_10_5_1","first-page":"94","article-title":"Merging the old skeletal biology with the new. 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