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 in skeletal development, cellular adhesion, and migration. Recent transcriptomic studies have shown an up-regulation in IGF1 expression in calvarial osteoblasts derived from patients with single-suture craniosynostosis (SSC). Up-regulation of the IGF1 signaling pathway is known to induce increased expression in a set of osteogenic markers that previously have been shown to be correlated to 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 may provide a target for therapeutic intervention.