Development is an orderly process that requires the timely activation and/or deactivation of specific regulatory elements that control cellular proliferation, differentiation and apoptosis. While many studies have defined factors that control developmental signaling, the role of intracellular reduction/oxidation (redox) status as a means to control differentiation has not been fully studied. Redox states of intracellular couples may play a very important role in regulating redox-sensitive elements that are involved in differentiation signaling into specific phenotypes. In human mesenchymal stem cells (hMSCs), which are capable of differentiating into many different types of phenotypes, including osteoblasts and adipocytes, glutathione (GSH), cysteine (Cys) and thioredoxin-1 (Trx1) redox potentials were measured during adipogenesis and osteogenesis. GSH redox potentials (Eh) during both osteogenesis and adipogenesis became increasingly oxidized as differentiation ensued, but the rate at which this oxidation occurred was unique for each process. During adipogenesis, Cys Eh became oxidized as adipogenesis progressed but during osteogenesis, it became reduced. Interestingly, intracellular Trx1 concentrations appeared to increase in both adipogenesis and osteogenesis, but the Eh was unchanged when compared to undifferentiated hMSCs. These data show that hMSC differentiation into either adipocytes of osteoblasts corresponds to a unique redox state profile, suggesting that differentiation into specific phenotypes are likely regulated by redox states that are permissive to a specific developmental process.
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