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Jidong Yan , Yuanxu Guo , Yao Fei , Rui Zhang , Yan Han , and Shemin Lu
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
Acta Biochim Biophys Sin 2017, 49: 110–118; doi: 10.1093/abbs/gmw125
Glutathione peroxidase 1 (GPx1) is a selenium (Se)-containing protein and is induced in cartilage formation. GPx1 eliminates reactive oxygen species (ROS), which are required for chondrogenic induction. The physiological properties of GPx1 in cartilage and the redox mechanisms involved are not known. The effects of GPx1 on chondrogenic differentiation of ATDC5 cells were examined through short hairpin RNA-mediated gene silencing. The results demonstrated that GPx1 knockdown impaired gene expression of sex determining region Y-box 9, collagen II (Col II), and aggrecan. GPx1 knockdown suppressed the accumulation of cartilage glycosaminoglycans (GAGs) and the proliferation of chondrocyte. GPx1 knockdown also induced cell apoptosis. However, cell sensitivity toward exogenous oxidative stress was not increased after GPx1 knockdown. Unexpectedly, GPx1 knockdown not only induced oxidative stress characterized by the increased production of ROS but also caused reductive stress indicated by an elevation of glutathione (GSH)/oxidized GSH (GSSG) ratio. Furthermore, GPx1 knockdown-mediated reductive and oxidative stress could be antagonized by a thiol-oxidizing agent diamide and a thiol-containing compound N-acetylcysteine (NAC), respectively. Moreover, NAC attenuated GPx1 knockdown-induced cell apoptosis, while diamide prevented GPx1 knockdown-suppressed chondrocyte proliferation. Finally, diamide but not NAC could rescue GPx1 knockdown-mediated impaired chondrogenic differentiation. In summary, GPx1 is essential for chondrogenic induction in ATDC5 cells mainly through modulation of intracellular GSH/GSSG ratio, rather than an antioxidant enzyme to detoxify ROS. In addition, GPx1 knockdown-induced impaired chondrogenesis may participate in the pathogenesis of the endemic osteoarthropathy due to Se deficiency. These observations offer novel insights for the development of therapeutic target during cartilage degeneration.
GPx1 knockdown inhibits chondrogenic differentiation
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