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论文题目: IL-12p40 impairs mesenchymal stem cell-mediated bone regeneration via CD4(+) T cells
英文论文题目: IL-12p40 impairs mesenchymal stem cell-mediated bone regeneration via CD4(+) T cells
第一作者: Xu, JJ; Wang, YY; Li, J; Zhang, XD; Geng, YY; Huang, Y; Dai, KR; Zhang, XL
英文第一作者: Xu, JJ; Wang, YY; Li, J; Zhang, XD; Geng, YY; Huang, Y; Dai, KR; Zhang, XL
联系作者: Dai, KR; Zhang, XL (reprint author), Inst Hlth Sci, Key Lab Stem Cell Biol, Room 1230 116 Mail Box,Life Sci Bldg Block A, Shanghai 200031, Peoples R China.
英文联系作者: Dai, KR; Zhang, XL (reprint author), Inst Hlth Sci, Key Lab Stem Cell Biol, Room 1230 116 Mail Box,Life Sci Bldg Block A, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 23
期: 12
页码: 1941-1951
摘要: Severe or prolonged inflammatory response caused by infection or biomaterials leads to delayed healing or bone repair failure. This study investigated the important roles of the proinflammatory cytokines of the interleukin-12 (IL-12) family, namely, IL-12 and IL-23, in the inflammation- mediated inhibition of bone formation in vivo. IL-12p40(-/-) mice lacking IL-12 and IL-23 exhibited enhanced bone formation. IL-12 and IL-23 indirectly inhibited bone marrow mesenchymal stem cell (BMMSC) differentiation by stimulating CD4(+) T cells to increase interferon gamma (IFN-gamma) and IL-17 levels. Mechanistically, IL-17 synergistically enhanced IFN-gamma-induced BMMSC apoptosis. Moreover, INF-gamma and IL-17 exerted proapoptotic effects by upregulating the expression levels of Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as by activating the caspase cascade in BMMSCs. IL-12p40 depletion in mice could promote ectopic bone formation. Thus, IL-12p40 is an attractive therapeutic target to overcome the inflammation- mediated inhibition of bone formation in vivo.
英文摘要: Severe or prolonged inflammatory response caused by infection or biomaterials leads to delayed healing or bone repair failure. This study investigated the important roles of the proinflammatory cytokines of the interleukin-12 (IL-12) family, namely, IL-12 and IL-23, in the inflammation- mediated inhibition of bone formation in vivo. IL-12p40(-/-) mice lacking IL-12 and IL-23 exhibited enhanced bone formation. IL-12 and IL-23 indirectly inhibited bone marrow mesenchymal stem cell (BMMSC) differentiation by stimulating CD4(+) T cells to increase interferon gamma (IFN-gamma) and IL-17 levels. Mechanistically, IL-17 synergistically enhanced IFN-gamma-induced BMMSC apoptosis. Moreover, INF-gamma and IL-17 exerted proapoptotic effects by upregulating the expression levels of Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as by activating the caspase cascade in BMMSCs. IL-12p40 depletion in mice could promote ectopic bone formation. Thus, IL-12p40 is an attractive therapeutic target to overcome the inflammation- mediated inhibition of bone formation in vivo.
刊物名称: CELL DEATH AND DIFFERENTIATION
英文刊物名称: CELL DEATH AND DIFFERENTIATION
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学科: Biochemistry & Molecular Biology; Cell Biology
英文学科: Biochemistry & Molecular Biology; Cell Biology
影响因子: 8.339
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论文类别: Article
英文论文类别: Article
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