Cytokine and hormonal regulation of bone marrow immune cell Wnt10b expression
نویسندگان
چکیده
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 TNFα 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 TNFα, we assessed Wnt10b expression by flow cytometry under estrogen- and TNFα-deficient conditions. METHODS Effects of TNFα was determined in male and female C57BL/6 wildtype and TNFα 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%). TNFα 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 TNFα on Wnt10b were observed only in males. In contrast to TNFα, 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.
منابع مشابه
Effect of IL-27 on activity of bone marrow NK cells of patient with B-chronic lymphocytic leukemia in vitro
Introduction: Functional defect in immune cells is the prominent feature in hematological malignancies that lead to the expansion of tumor cells. Using immunostimulatory cytokines is one of the new therapeutic approaches. This study aimed to investigate the effect of IL-27 on the activity of bone marrow-NK cells of chronic lymphocytic leukemia (CLL) patients in vitro. Materials and Methods: 10 ...
متن کاملAnalysis of MiRNA-17 and MiRNA-146 Expression During Differentiation of Spermatogonial Stem Like Cells Derived from Mouse Bone Marrow Mesenchymal Stem Cells
In vitro derivation of germ cells from different stem cells sources has been challenging in the treatment of male infertility. MicroRNAs (miRNAs) have an essential role in gene expression at post-transcriptional level. The aim of this research was to find more about miRNA-17 and miRNA-146 expression during differentiation of spermatogonial stem cell like cells (SSC like cells) from mouse bone m...
متن کاملIn vitro Effect of Pomalidomide on Bone Marrow Mononuclear Cells from Multiple Myeloma Patients
Background: Many features of anticancer drugs, including cytotoxicity and/or cytokine induction, are studied using cell lines orhuman blood leukocytes. However, in a disease such as multiple myeloma, most cancerous cells are resided within bone marrowmononuclear cells. In the present study, we investigated the effect of pomalidomide on apoptosis and IL-2 production of bonemarrow mononuclear cel...
متن کاملThe effect of bone marrow-derived mesenchymal stem cells to induce PD-L1 molecule on splenic lymphocytes
Background: Mesenchymal stem cells are non-hematopoietic stromal cells that are used in the treatment of many chronic and autoimmune diseases by modulating the immune system. Due to the limitations of using autologous mesenchymal stem cells, the use of allogeneic stem cells is a promising therapeutic approach in the treatment of immunological disorders. This study aimed to investigate the abili...
متن کاملMild hypoxia and human bone marrow mesenchymal stem cells synergistically enhance expansion and homing capacity of human cord blood CD34+ stem cells
Objective(s): Cord blood (CB) is known as a valuable source of hematopoietic stem cells (HSC). Identifying strategies that enhance expansion and maintain engraftment and homing capacity of HSCs can improve transplant efficiency. In this study, we examined different culture conditions on ex vivo expansion and homing capacity of CB-HSCs. Materials and Methods: In this study, 4-5 different units o...
متن کامل