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首页> 外文期刊>Cellular Signalling >Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway
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Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway

机译:咖啡因通过p38 MAP激酶/ Mitf和DC-STAMP / CtsK和TRAP途径增强破骨细胞的分化和成熟

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The consumption of caffeine from some common beverages has been associated with low bone mass by inducing urinary calcium loss and deceasing bone mineral density. However, the effect of caffeine on osteoclast differentiation is still unclear. Here, we demonstrate that caffeine directly enhances osteoclast differentiation and maturation. TRAP staining showed that the number of larger (>. 100. μm) osteoclastic cells as well as of TRAP-positive multinucleated cells was increased by caffeine treatment. Among the MAP kinases, caffeine specifically activated p38 MAP kinase, which in turn, controlled osteoclast differentiation and maturation. This is evidenced by the abolishment of activated p38 MAP kinase by pretreatment with SB203580, a p38-specific inhibitor, resulting in suppressed osteoclast differentiation and maturation that should be increased by caffeine. Caffeine significantly induced the expression of Mitf and pretreatment with SB203580 markedly suppressed the expression of Mitf induced by caffeine. Whereas it failed to regulate the expression of NFATc1 and Oscar, the expressions of Cathepsin K and TRAP were induced by caffeine treatment in primary preosteoclasts. Real-time PCR and luciferase assays showed that the increase of osteoclastic cell-cell fusion by caffeine was through the transcriptional up-regulation of DC-STAMP expression but not of Atp6v0d2. These results strongly suggest that caffeine directly enhances osteoclast differentiation and maturation through p38 MAP kinase activation, thus inducing Mitf expression and transcriptional activation of DC-STAMP, and finally CtsK and TRAP.
机译:通过诱导尿钙流失和骨矿物质密度降低,从某些普通饮料中摄入咖啡因与骨量低有关。但是,咖啡因对破骨细胞分化的作用仍不清楚。在这里,我们证明咖啡因直接增强破骨细胞的分化和成熟。 TRAP染色显示,咖啡因处理可增加较大(>。100.μm)破骨细胞以及TRAP阳性多核细胞的数量。在MAP激酶中,咖啡因可特异性激活p38 MAP激酶,进而控制破骨细胞的分化和成熟。这可以通过用p38特异性抑制剂SB203580预处理取消激活的p38 MAP激酶来证明,这可以抑制破骨细胞的分化和成熟,而咖啡因应增加破骨细胞的分化和成熟。咖啡因可显着诱导Mitf的表达,SB203580预处理可显着抑制咖啡因诱导的Mitf的表达。尽管它不能调节NFATc1和Oscar的表达,但通过咖啡因处理可在原骨破骨细胞中诱导组织蛋白酶K和TRAP的表达。实时荧光定量PCR和荧​​光素酶测定表明,咖啡因增加了破骨细胞与细胞的融合,这是由于DC-STAMP表达的转录上调,而不是Atp6v0d2的转录上调。这些结果强烈表明咖啡因通过p38 MAP激酶激活直接增强破骨细胞的分化和成熟,从而诱导Mitf表达和DC-STAMP的转录激活,最后诱导CtsK和TRAP。

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