The Effects of Androgens for Mouse Embryonic Stem Cells Differentiated into Mineralized Osteoblasts

Bone is constantly undergoing remodeling to cope with growth, repair, and mechanical loading. This process is characterised by a balance between the synthesis of bone matrix by the osteoblasts and degradation by osteoclasts. A disruption in this balance can result in pathological states, highlighted by osteoporosis, where the resulting loss of bone density predisposes individuals to serious fractures. Accordingly, there is currently great interest in studying the mechanisms governing osteoblast growth and differentiation. The recent identification of osteogenesis-related transcription factors and osteoblast-specific markers has led to a rapid advancement in understanding the process of osteoblast differentiation. Many growth factors and cytokines have been shown to promote the differentiation of osteoblasts, including insulin-like growth factor-1 and IL-6 related cytokines etc. On the other hand, the estrogens and androgens, belonged to sex hormones, were also shown to promote the differentiation of osteoblasts. Many of the studies on osteoblast differentiation were performed either on cultured preosteoblastic cells, or bone-marrow derived progenitor cells. These approaches have been invaluable in identifying key steps of the differentiation process. However, the early steps of osteoblast differentiation remain to be identified. In this proposal, we examine the osteoblast differentiation process in murine embryonic stem cells and use the model system to explore the effects of androgens on osteogenesis. The embryonic stem (ES) cell, derived from inner cell mass (ICM) within the blastocyst, as the most pluripotent stem cell, the can form almost all tissue types. Due to their unique character, investigators can use embryonic stem cells to examine potential mechanisms of genetic engineering, an avenue that will also offer a better understanding of normal gene function and control through manipulation of stem cell-derived cells and study cell differentiation. In our preliminary results, we have well learnt how to maintain the mouse ES cells in a state of undifferentiation or induce them to differentiate into specific ES-derived cells under specific culture conditions. Subsequently, in this proposal, we will to explore the effects of androgens for mouse ES cells, differentiated into mineralized osteoblasts. We will use histochemical analysis, biochemical determinations, immunofluorescence stain and real-time qualitative PCR as tools to investigate these specific aims.

Project ID:PC9308-1109
External Project ID:NSC93-2314-B182-084