Abstract
Apoptosis of osteoblasts induced by glucocorticoid (GC) has been identified as a main cause of osteoporosis, bone loss and fractures, and the oxidative stress was found as an important contributor. Therefore, natural or synthetic agents with antioxidant activities can antagonize GCs-induced apoptosis in osteoblasts, and thus demonstrate the potential application to reverse osteoporosis. In this study, we showed that, indole-3-carbinol (I3C), a natural product found in broadly consumed plants of the Brassica genus, could block the cytotoxic effects of dexamethasone (Dex), and elucidated the underlying molecular mechanisms. Firstly, we showed that, I3C could effectively suppress Dex-induced cytotoxicity and apoptotic cell death in osteoblastic cells, as evidenced by the decrease in Sub-G1 cell population. Treatment of the cells with Dex resulted in activation of caspase-3/-8/-9 and subsequent cleavage of PARP, which was also effectively blocked by co-incubation of I3C. Moreover, exposure to Dex triggered a rapid onset and time-dependent superoxide overproduction in osteoblastic cells, which was effectively suppressed by addition of I3C. Excess intracellular ROS induced by Dex significantly suppressed the expression levels of Nrf2...Continue Reading
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