Doxorubicin induces bone loss and modifies multiple cell populations in vivo – Implications for modelling of bone metastasis

Figures

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  Fig. 1. Effects of doxorubicin on bone structure 7-week-old female BALB/c (left panels) and BALB/c Nude (right panels) mice received either saline (CON) or doxorubicin (DOX, 4 or 6 mg/kg) weekly up to day 24. Effects were compared to saline for the following: A) trabecular bone volume (BV/TV%), B) trabecular number (Tn/mm−1), C) trabecular bone separation (mm), D) trabecular bone thickness (mm), E) Cortical bone volume (mm). F) Shows examples of 3D reconstructed uCT images Data are shown as Mean ± SD, n = for 8 for 4 mg/kg DOX and n = 5 for 6 mg/kg DOX. ** p ≤ 0.01, *** p ≤ 0.001 and **** p ≤ 0.0001, ns is non-significant.

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  Fig. 2. Comparison of bone marrow cell populations between immunocompetent and immunocompromised mice. Comparison of A) LSK Cell and B) LK Cell data as % of live cells, isolated from BALB/c (red) and BALB/c Nude (blue) bone marrow, C) B Lymphocytes, D) CD8+ T Lymphocytes, E) CD4+ T Lymphocytes, F) Macrophages, G) Monocytes and H) Neutrophils as % of live CD45+ cells. T-Test was used for statistical analysis, ns is non-significant, *** is p < 0.001, **** is p < 0.0001 and data show Mean ± SD, n = 8 for BALB/c and BALB/c Nude mice. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

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  Fig. 3. Effects of doxorubicin on the hematopoietic stem cells and their progenitors in BALB/c and BALB/c Nude mice. Flow cytometry analysis of bone marrow cell populations of 7-week-old female BALB/c and BALB/c Nude mice treated with either saline (CON.) or 6 mg/ kg doxorubicin (DOX.) Effects on the A) LSK cells and B) LK cells (% of live cells) were compared using T-Test. ns is non-significant, * ≤ 0,05, *** ≤0.001 and **** ≤0.0001. Data shown as Mean ± SD n = for 8 for all groups.

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  Fig. 4. Effects of doxorubicin on bone marrow immune cell populations in BALB/c and BALB/c Nude mice. Flow cytometry analysis of bone marrow cell populations of 7-week-old female BALB/c and BALB/c Nude mice treaded with either saline (CON.) or 6 mg/ kg doxorubicin (DOX.) Effects (% of live CD45+ cells) on A) B cells, B) CD8+ T cells, C) CD4+ T cells, D) macrophages, E) monocytes and F) neutrophils were compared using T-Test. ns is non-significant, * ≤0.05, ** ≤0.01, *** ≤0.001 and **** ≤0.0001. Data shown as Mean ± SD n = for 8 for all groups.