Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into various types of cells including chondrocytes, osteoblasts and adipocytes. Since these types of cells are simultaneously derived from the same precursor cell, adipogenesis and osteoblastogenesis are thought to be counter-related. It is well-known that chronic treatment of steroid can induce Cushings syndrome which has phenotypes like visceral adiposity and osteoporosis. Cell fate of differentiation into either adipocytes or osteoblasts is one of the critical factors of these symptoms, but the molecular mechanism of cell fate decision of MSCs under the streroid treatment is unclear. Recently, we showed that Dexras1 mediates glucocorticoids and IGF-I signaling followed by MAPK activation and results in increased adipogenesis while its abolishment decreases adipogenesis. Now we established that lack of Dexas1 exhibited increased osteogenesis in mesenchymal stem cells including both bone marrow derived stem cells (BMSCs) and mouse embryonic fibroblasts (MEFs). Corroborative to our previous data, decreased adipogenesis in MSCs was also observed in the absence of Dexras1. Despite less dramatic change in differentiation, it is also shown that lessened mature osteoblasts in Dexras1-overexpressing preosteoblast cell line, MC3T3-E1, down regulating Smad signaling in the early period of differentiation. Furthermore, we found that Dexras1 is involved in increased central obesity associated with chronic treatment of steroids but rescued steroid-induced osteoporosis in mouse model treated with dexamethasone for 8 weeks followed by increased gene expression related to osteoblast in the murine bone. Above all these results, we suggest that Dexras1 is a key molecule which stimulates adiposity and down regulates osteogenesis via counter regulating action.
20 - 23 May 2017
European Society of Endocrinology