Figure 2
Figure 2. Blockade of TBI-induced c-MPL–dependent megakaryocyte endosteal migration abrogates niche osteoblast expansion post-TBI. (A) H&E sections (63×) of WT (left panels) and mpl−/− (right panels) metaphyseal bone (BO) and BM at baseline (top) and 48 hours post-TBI in the presence (bottom) or absence (middle) of CD41 blockade, demonstrating a single layer of endosteal osteoblasts at baseline followed by proliferation and expansion of endosteal osteoblasts in WT BM 48 hours post-TBI that is markedly attenuated by c-MPL deficiency, but not CD41 blockade. (B) Quantitative scoring analysis of osteoblast layer number (mean ± SEM) at baseline in WT and mpl−/− mice (n = 5 mice each); in WT mice receiving TBI only (n = 19), or blockade of c-MPL (n = 10), CXCR4, or CD41 (n = 5 each); and in mpl−/− mice receiving TBI only (n = 19) or TBI plus blockade of CXCR4 or CD41 (n = 5 each). *P < .01 vs unirradiated group within same strain, +P < .05 vs WT mice receiving TBI only in TBI-treated groups (comparisons performed by 1-way ANOVA and Dunnett posttest analysis).

Blockade of TBI-induced c-MPL–dependent megakaryocyte endosteal migration abrogates niche osteoblast expansion post-TBI. (A) H&E sections (63×) of WT (left panels) and mpl−/− (right panels) metaphyseal bone (BO) and BM at baseline (top) and 48 hours post-TBI in the presence (bottom) or absence (middle) of CD41 blockade, demonstrating a single layer of endosteal osteoblasts at baseline followed by proliferation and expansion of endosteal osteoblasts in WT BM 48 hours post-TBI that is markedly attenuated by c-MPL deficiency, but not CD41 blockade. (B) Quantitative scoring analysis of osteoblast layer number (mean ± SEM) at baseline in WT and mpl−/− mice (n = 5 mice each); in WT mice receiving TBI only (n = 19), or blockade of c-MPL (n = 10), CXCR4, or CD41 (n = 5 each); and in mpl−/− mice receiving TBI only (n = 19) or TBI plus blockade of CXCR4 or CD41 (n = 5 each). *P < .01 vs unirradiated group within same strain, +P < .05 vs WT mice receiving TBI only in TBI-treated groups (comparisons performed by 1-way ANOVA and Dunnett posttest analysis).

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