Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway
Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway
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DOI：
10.1016/j.cellsig.2013.02.015
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发表时间：
2013-05-01
影响因子：
4.8
通讯作者：
Lee, Na Kyung
中科院分区：
文献类型：
--
作者：
Choi, Jiwon;Choi, So Yoen;Lee, Na Kyung
从一些常见的饮料中摄入咖啡因与低骨量有关，通过诱导尿钙流失和降低骨矿物质密度。然而，咖啡因对破骨细胞分化的影响仍不清楚。在这里，我们证明，咖啡因直接促进破骨细胞的分化和成熟。TRAP染色显示，较大（>100 μ m）的骨细胞以及TRAP阳性多核细胞的数量增加，咖啡因治疗。在MAP激酶中，咖啡因特异性激活p38 MAP激酶，其反过来控制破骨细胞的分化和成熟。这一点可以通过用SB 203580（一种p38特异性抑制剂）预处理消除活化的p38 MAP激酶来证明，这导致了破骨细胞分化和成熟受到抑制，而咖啡因应该增加这种抑制。咖啡因可显著诱导Mitf的表达，SB 203580预处理可显著抑制咖啡因诱导的Mitf表达。咖啡因对NFATc 1和Oscar的表达无调节作用，但可诱导破骨细胞表达Cathepsin K和TRAP。实时荧光定量PCR和荧光素酶检测结果表明，咖啡因通过上调DC-STAMP的表达而非Atp 6v 0 d2的表达来促进骨细胞-细胞融合。这些结果强烈表明，咖啡因直接增强破骨细胞的分化和成熟，通过p38 MAP激酶激活，从而诱导Mitf的表达和DC-STAMP的转录激活，并最终CtsK和TRAP。(C)2013 Elsevier Inc. All rights reserved.
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 mu m) 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. (C) 2013 Elsevier Inc. All rights reserved.