KMID : 0620920190510060062
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Experimental & Molecular Medicine 2019 Volume.51 No. 6 p.62 ~ p.62
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Peroxiredoxin II negatively regulates BMP2-induced osteoblast differentiation and bone formation via PP2A C¥á-mediated Smad1/5/9 dephosphorylation
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Kim Kyeong-Min
Kim Do-Young Lee Dong-Seok Kim Jung-Woo Koh Jeong-Tae Kim Eun-Jung Jang Tae-Jung
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Abstract
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Peroxiredoxin II (Prx II), an antioxidant enzyme in the Prx family, reduces oxidative stress by decreasing the intracellular ROS levels. Osteoblast differentiation is promoted by bone morphogenetic protein 2 (BMP2), which upregulates the expression of osteoblast differentiation marker genes, through Smad1/5/9 phosphorylation. We found that Prx II expression was increased by a high dose of lipopolysaccharide (LPS) but was not increased by a low dose of LPS. Prx II itself caused a decrease in the osteogenic gene expression, alkaline phosphatase (ALP) activity, and Smad1/5/9 phosphorylation induced by BMP2. In addition, BMP2-induced osteogenic gene expression and ALP activity were higher in Prx II knockout (KO) cells than they were in wild-type (WT) cells. These inhibitory effects were mediated by protein phosphatase 2A C¥á (PP2A C¥á), which was increased and is known to induce the dephosphorylation of Smad1/5/9. The overexpression of Prx II increased the expression of PP2A C¥á, and PP2A C¥á was not expressed in Prx II KO cells. Moreover, PP2A C¥á reduced the level of BMP2-induced osteogenic gene expression and Smad1/5/9 phosphorylation. LPS inhibited BMP2-induced Smad1/5/9 phosphorylation and the suppressed phosphorylation was restored by the PP2A inhibitor okadaic acid (OA). Bone phenotype analyses using microcomputed tomography (¥ìCT) revealed that the Prx II KO mice had higher levels of bone mass than the levels of the WT mice. We hypothesize that Prx II has a negative role in osteoblast differentiation through the PP2A-dependent dephosphorylation of Smad1/5/9.
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KEYWORD
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Cell signalling, Mesenchymal stem cells
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