Improved ROS accounts for the disruption of mitochondrial homeostasis and the depolarization of mitochondrial membrane potential which plays a crucial role in maintaining cellular energy and metabolic rate balance. The dysfunction of the mitochondria may induce mobile apoptosis JZL184 clinical trial by causing the release cytochrome c that triggers caspase activation. In agreement, our study also unveiled that exposure to homocysteine can increase intracellular ROS stage and in turn cause the depolarization of mitochondrial membrane potential in BMSCs. To determine that ROS is necessary for homocysteine induced improvements of BMSCs, two anti-oxidants NAC and DMTU were used to prevent intracellular ROS accumulation induced by homocysteine. The results demonstrated that both DMTU and NAC can reverse the apoptosis of BMSCs induced by homocysteine. In addition, Gene expression the inhibition of intracellular ROS with antioxidants also attenuated homocysteine induced depolarization of mitochondrial membrane potential, indicating ROS mediate mitochondrial damage contributes to the apoptosis of BMSCs. The MAPK signaling p38 MAPK, JNK and ERK is absolutely implicated in the induction of apoptosis in a reaction to oxidant stress signals. Particularly, the activated p38 MAPK, JNK and ERK were frequently observed involved in ROSmediated cellular apoptosis. Recent studies also noted that ROS mediated activation of p38 and JNK induce the phosphorylation of Bcl 2, which leads to mitochondrial apoptotic cell death. In this review, we further investigated the role of MAPK signaling in ROS mediated mitochondrial apoptotic cell death brought about by homocysteine. The outcomes showed the impediment of JNK with its specific inhibitor can abrogate homocysteineinduced mitochondrial apoptotic cell death, but p38 MAPK and ERK specific inhibitors did not affect homocysteine induced apoptosis of BMSCs. It shows that the activation of JNK is involved in homocysteine caused apoptotic morphological changes. We FDA approved HDAC inhibitors also detected the expression of caspase 3, p53 and Bcl 2 to confirm if homocysteine contributes to the apoptosis of BMSCs. The results confirmed that homocysteine treatment caused a rise of cleave caspase 3 protein and decrease of Bcl 2 protein in BMSCs, indicating the purpose of homocysteine in BMSCs. The concentration of homocysteine that people used in the cultured cells is higher-than plasma homocysteine level under physiological condition, which could maybe not be avoided because the metabolism of homocysteine was significantly upregulated in the cells in culture as described in previous studies. Actually, the identical or high level of homocysteine has been trusted in a variety of previous investigations. More over, a higher concentration of homocysteine is required to mimics the future effects of minor or middle increase of homocysteine in human bodies. Taken together, we found that increased homocysteine level increased intracellular ROS production and caused the depolarization of mitochondrial membrane potential, and in turn resulted in the apoptosis of BMSCs via activating JNK indication.