Activation of the IGF1 pathway mediates changes in cellular contractility and motility in single-suture craniosynostosis

IGF1 通路激活介导单缝颅缝早闭细胞收缩力和运动力的变化

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作者:Zeinab Al-Rekabi, Marsha M Wheeler, Andrea Leonard, Adriane M Fura, Ilsa Juhlin, Christopher Frazar, Joshua D Smith, Sarah S Park, Jennifer A Gustafson, Christine M Clarke, Michael L Cunningham, Nathan J Sniadecki

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.

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