17β-Estradiol Induces the Proliferation of Hematopoietic Stem Cells by Promoting the Osteogenic Differentiation of Mesenchymal Stem Cells

The process of hematopoiesis is associated with hematopoietic stem cells (HSCs) and the hematopoietic microenvironment. Osteoblasts, derived from mesenchymal stem cells (MSCs), are one of the most important components in the hematopoietic microenvironment. Osteoblasts secrete a variety of cytokines including interleukin-6 (1-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), thereby regulating the biological activities of HSCs. It has been shown that hematopoiesis dysfunction can be induced by estrogen-deficiency through the exhaustion of HSCs. However, the effect of estrogen on the proliferation of HSCs is not fully understood. The aim of this study was to investigate the role of estradiol in the process of hematopoiesis, especially regarding the proliferation of HSCs in vitro. Bone marrow-derived MSCs and HSCs were isolated from 3-month-old female Sprague-Dawley rats. Mineralization ability and osteocalcin assays demonstrated that treatment with 17 beta-estradiol (E2) significantly enhanced the osteogenic differentiation of MSCs. HSCs and MSCs were then cocultured with or without E2 treatment. Colony forming assays demonstrated that E2 increased the number of colony forming units-granulocyte/ macrophage in a dose-dependent manner when HSCs were co-cultured with MSCs in Osteogenic Medium that is suitable for the in vitro osteogenic differentiation. Further, increased concentrations of GM-CSF and IL-6 were detected by enzyme linked immunosorbent assay (ELISA). These results indicate that E2 induces the proliferation of HSCs, which depends on the promotion of osteogenic differentiation of MSCs, and that process is mediated by both GM-CSF and IL-6.