Targeting of C-ROS-1 Activity Using a Controlled Release Carrier to Treat Craniosynostosis in a Preclinical Model of Saethre-Chotzen Syndrome

Figure 2

Local administration of CMC microdisk infused with crizotinib reduces calvarial bone formation and the incidence of premature coronal suture fusion in 20 -day-old mice. (a) Representative μCT images of coronal sutures (arrows) of 20-day-old mouse skulls following local implantation of CMC microdisks containing either 0.1% DMSO or crizotinib at different concentrations (1-4 μM) at P8. (b) Representative images of Masson’s trichome-stained coronal suture sections (white arrow: closed sutures, black arrow: open sutures) from 20-day-old mice following local implantation a CMC microdisc containing either 0.1% DMSO or crizotinib at different concentrations (1–4 μM), scale bar = 100 μm (100× magnification). (c) Number of open coronal sutures versus closed coronal sutures in crizotinib-treated mice at P20 (n = 12 per the treatment group). (d) Histomorphometric analysis of mineralized bone formed of locally treated coronal sutures. Values are the mean ± SEM, one-way ANOVA with Tukey’s multiple comparisons, DF = 3, F = 4.567 (1 μM Crizo, ; 2 μM Crizo, ; 4 μM Crizo, ), n = 8–11 coronal sutures/treatment group. (e) Histomorphometric analysis of bone volume fraction (bone volume/total volume) of locally treated coronal sutures. Values are the mean ± SEM, , one-way ANOVA with Tukey’s multiple comparisons, DF = 3, F = 1.637 (1 μM Crizo, ; 2 μM Crizo, ; 4 μM Crizo, ), n = 9–14 coronal sutures/treatment group.

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