Transdifferentiation from Adipogenic bone Marrow Derived Stromal Cell to Osteoblast / 대한정형외과연구학회지

ABSTRACT

PURPOSE: The inhibition of marrow adipogenesis with a concomitant increase in osteogenesis could be a therapeutic target by preventing the increase of adipocyte formation or diverting the preexisting adipocytes. The changes of morphology and gene expression, and the role of Mitogen-Activated Protein Kinase (MAPK) was evaluated in the process of transdifferentiation from adipogenic MSC to osteogenic MSC. MATERIALS AND METHODS: Human mesenchymal stem cells were isolated from bone marrow and cultured in adipogenic medium in the presence of 25 muM troglitazone for 14 days. Then cells were cultured in osteogenic medium for 28 days. To find out the mechanisms responsible for transdifferentiation, we performed RT-PCR, several stains, alkaline phosphatase activity, and western blot analysis. RESULTS: In RT-PCR, when adipogenic mesenchymal stem cells were cultured in osteogenic medium, mRNA levels of the adipogenic genes (LPL, aP2, and PPAR-nu) were decreased and those of the osteogenic genes (collagen type I and osteocalcin) were increased. The adipogenic MSC in osteogenic medium for 28 days exhibited a fibroblastic appearance and were stained positively with von Kossa and alkaline phosphatase. In western blot analysis, we found that ERK phosphorylation was inhibited in the early stage of adipogenesis. CONCLUSION: In this study, adipogenic mesenchymal stem cells were shown to differentiate into the osteogenic MSC under appropriate culture conditions. The evidence of the transdifferentiation of human mesenchymal stem cells suggests that it could be a therapeutic target in osteoporosis.