Plasticity in adipogenesis and osteogenesis of human mesenchymal stem cells.

We established a cell culture system of human mesenchymal stem cells that allows not only for osteogenic and adipogenic differentiation but also for transdifferentiation between both cell lineages. Committed osteoblasts were transdifferentiated into adipocytes with losing osteogenic but highly expressing adipogenic markers. Adipocytes were transdifferentiated into osteoblasts with most of the resulting cells showing osteogenic but some still displaying adipogenic markers apparently not responding to the reprogramming stimulus. Comparing transdifferentiated adipocytes with committed osteoblasts by microarray analysis revealed 258 regulated transcripts, many of them associated with signal transduction, metabolism, and transcription but mostly distinct from established inducing factors of normal adipogenic and osteogenic differentiation, respectively. The regulation pattern of 20 of 22 selected genes was confirmed by semiquantitative RT-PCR. Our results indicate that the plasticity between osteogenesis and adipogenesis extends into the differentiation pathways of both cell lineages and may contribute to the age-related expansion of adipose tissue in human bone marrow.