title: Activation of the IGF1 pathway mediates changes in cellular contractility and motility in single-suture craniosynostosis.
abstract: Insulin growth factor 1 (IGF1) is a major anabolic signal that is essential during skeletal development, cellular adhesion and migration. Recent transcriptomic studies have shown that there is an upregulation in IGF1 expression in calvarial osteoblasts derived from patients with single-suture craniosynostosis (SSC). Upregulation of the IGF1 signaling pathway is known to induce increased expression of a set of osteogenic markers that previously have been shown to be correlated with contractility and migration. Although the IGF1 signaling pathway has been implicated in SSC, a correlation between IGF1, contractility and migration has not yet been investigated. Here, we examined the effect of IGF1 activation in inducing cellular contractility and migration in SSC osteoblasts using micropost arrays and time-lapse microscopy. We observed that the contractile forces and migration speeds of SSC osteoblasts correlated with IGF1 expression. Moreover, both contractility and migration of SSC osteoblasts were directly affected by the interaction of IGF1 with IGF1 receptor (IGF1R). Our results suggest that IGF1 activity can provide valuable insight for phenotype-genotype correlation in SSC osteoblasts and might provide a target for therapeutic intervention.
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA 98101, USA.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Al-Rekabi
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
authors.forename: Marsha M
authors.initials: MM
authors.lastname: Wheeler
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leonard
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98105, USA.
authors.forename: Adriane M
authors.initials: AM
authors.lastname: Fura
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ilsa
authors.initials: I
authors.lastname: Juhlin
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Frazar
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA 98101, USA.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Park
authors.affiliation: Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA 98101, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gustafson
authors.affiliation: Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA 98101, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Clarke
authors.affiliation: Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA 98101, USA Division of Craniofacial Medicine and the Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cunningham
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA Department of Bioengineering, University of Washington, Seattle, WA 98105, USA nsniadec@uw.edu.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Sniadecki
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Calvarial osteoblast; Cell migration; IGF1; IGF1R; Single-suture craniosynostosis; Traction force