| First Author | Collins FL | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0181979 |
| PubMed ID | 28800644 | Mgi Jnum | J:245740 |
| Mgi Id | MGI:5915354 | Doi | 10.1371/journal.pone.0181979 |
| Citation | Collins FL, et al. (2017) Cytokine and hormonal regulation of bone marrow immune cell Wnt10b expression. PLoS One 12(8):e0181979 |
| abstractText | BACKGROUND & AIMS: Wnt10b is a crucial regulator of bone density through its ability to promote osteoblastogenesis. Parathyroid hormone has been shown to regulate Wnt10b expression in CD8+ T cells. However, the relative expression and other source(s) of Wnt10b in the bone marrow immune cells (BMICs) is unknown. Sex hormones and cytokines such as, estrogen and TNFalpha are critical regulators of bone physiology but whether they regulate BMIC Wnt10b expression is unclear. To determine the potential regulation of Wnt10b by estrogen and TNFalpha, we assessed Wnt10b expression by flow cytometry under estrogen- and TNFalpha-deficient conditions. METHODS: Effects of TNFalpha was determined in male and female C57BL/6 wildtype and TNFalpha knockout mice. Effect of estrogen was investigated 4, 6 and 8 weeks post-surgery in ovariectomized Balb/c mice. Intracellular Wnt10b was detected using goat anti-mouse Wnt10b and a conjugated secondary antibody and analyzed by flow cytometry. RESULTS: Wnt10b expression was sex- and lineage-specific. Females had 1.8-fold higher Wnt10b signal compared to males. Percent of Wnt10b+ myeloid cells was higher in females than males (8.9% Vs 5.4%) but Wnt10b+ lymphoid cells was higher in males than females (6.3% Vs 2.5%). TNFalpha ablation in males increased total BM Wnt10b expression 1.5-fold but significantly reduced the percentage of BM Wnt10b+ CD4+ T cells (65%), CD8+ T cells (59%), dendritic cells (59%), macrophages (56%) and granulocytes (52%). These effects of TNFalpha on Wnt10b were observed only in males. In contrast to TNFalpha, estrogen-deficiency had indirect effects on BMIC Wnt10b levels; reducing the average percentage of BM Wnt10b+ CD8+ T cells (25%) and granulocytes (26%) across an 8-week time course. CONCLUSION: Our results demonstrate unique cell type- and sex-dependent effects on BMIC Wnt10b expression. Together, our results reveal myeloid cells in the bone marrow as an important source of Wnt10b under complex hormonal and cytokine regulation. |
