Low-dose suspended graphene oxide nanosheets induce antioxidant response and osteogenic differentiation of bone marrow-derived mesenchymal stem cells via JNK-dependent FoxO1 activation.

Large bone defects caused by bone-related diseases and traumatic injuries can disrupt the self-healing potential of bone tissue. Mesenchymal stem cells (MSCs) are known as promising cell sources for bone tissue regeneration. Graphene oxide (GO), a derivative of graphene, has been recently used for controlling the differentiation of stem cells towards bone-forming cells. However, the effect of GO on the intracellular redox system in MSCs is still unknown. In this study, we found that low-dose GO nanosheets (0.1 μg mL-1) did not affect the viability and slightly increased the proliferation of BM-MSCs. Moreover, they could also maintain the redox balance by upregulating the antioxidant genes such as MnSOD and catalase during osteogenic differentiation. The osteoinductive and antioxidative effects of the low-dose GO nanosheets were regulated by the activation and nuclear localization of FoxO1, and its activation was dependent on the JNK activity. The blockade of JNK activity by SP600125 inhibited the nuclear translocation of FoxO1, and subsequently suppressed the osteogenic differentiation and antioxidant defense system of BM-MSCs. Overall, our results show that the osteoinductive and antioxidative effects of low-dose GO nanosheets occur through the activation of the JNK and FoxO1 signaling pathways.