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

Figure 4

Crizotinib treatment is reversible in mice by postnatal day 25. (a) Representative μCT images of coronal sutures (arrows) of 25-day-old mouse skulls following local implantation of CMC microdiscs containing either 0.1% DMSO or crizotinib at different concentrations (1–4 μM) at P8. (b) Representative images of Masson’s trichome-stained coronal sutures sections from 25-day-old mice following local implantation of CMC microdisc containing either 0.1% DMSO or 1, 2, or 4 μM of crizotinib at P8, scale bar = 100 μm (100×). (c) 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 = 2.63, (1 μM Crizo, ; 2 μM Crizo, ; 4 μM Crizo, ), n = 16–26 coronal sutures/treatment group. (d) Histomorphometric analysis of bone density (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 = 3.812 (1 μM Crizo, ; 2 μM Crizo, ; 4 μM Crizo, ), n = 16–26 coronal sutures/treatment group. (e) Representative μCT images of coronal sutures (arrows) for 25-day-old mouse skulls following local implantation of CollaCote sponge carriers containing either 0.1% DMSO or 4 μM crizotinib at P8. (f) Representative images of Masson’s trichome-stained coronal sutures sections from 25-day-old mice following local implantation of a CollaCote containing either 0.1% DMSO or 4 μM crizotinib at P8, scale bar = 100 μm (100×). (g) Histomorphometric analysis of mineralized bone formed of locally treated coronal sutures in mice treated with CollaCote containing either 0.1% DMSO or 4 μM crizotinib. Values are the mean ± SEM, , unpaired t-test, two-tailed (Crizo 4 μM, ), n = 14 coronal sutures/treatment group. (h) Histomorphometric analysis of bone density (bone volume/total volume) of locally treated coronal sutures in mice treated with CollaCote containing either 0.1% DMSO or 4 μM crizotinib. Values are the mean ± SEM, , unpaired t-test, two-tailed (Crizo 4 μM, ), n = 14 coronal sutures/treatment group.

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