Ascorbic acid promotes osteoclastogenesis from embryonic stem cells
Ascorbic acid promotes osteoclastogenesis from embryonic stem cells
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DOI：
10.1016/j.bbrc.2005.08.016
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发表时间：
2005-10-07
影响因子：
3.1
通讯作者：
Hayashi, SI
中科院分区：
文献类型：
--
作者：
Tsuneto, M;Yamazaki, H;Hayashi, SI
抗坏血酸(AA)是已知的调节细胞分化的物质；然而，AA对破骨细胞生成的影响，尤其是对其早期阶段的影响尚不清楚。为了研究AA在破骨细胞发育过程中的作用，我们建立了从胚胎干细胞诱导抗酒石酸酸性磷酸(TRAP)阳性破骨细胞的培养体系，该培养体系不含基质细胞系。在该培养体系中，在破骨细胞前体的发育过程中加入AA可显著增加TRAP阳性细胞的数量，而还原剂2-巯基乙醇、单甘油和二硫苏糖醇不能替代AA。在中胚层细胞发育的最初4天添加AA的效果比在后4天添加AA的效果更强。在培养的第4天，AA增加了细胞的总回收率和破骨细胞前体的频率。用抗Flk-1抗体对破骨细胞前体细胞进行磁性分选，第4天，加入AA后，Flk-1阳性细胞比例增加，但血小板衍生生长因子受体α阳性细胞比例不增加。这些结果提示，AA可能通过增加Flk-1阳性细胞而促进ES细胞的破骨细胞生成，进而产生破骨细胞前体。(C)2005 Elsevier Inc.保留所有权利。
Ascorbic acid (AA) is known to regulate cell differentiation; however, the effects of AA on osteoclastogeriesis, especially on its early stages, remain unclear. To examine the effects of AA throughout the process of osteoclast development, we established a culture system in which tartrate-resistant acid phosphate (TRAP)-positive osteoclasts were induced from embryonic stem cells without stromal cell lines. In this culture system, the number of TRAP-positive cells was strongly increased by the addition of AA during the development of osteoclast precursors, and reducing agents, 2-mercaptoethanol, monothioglycerol, and dithiothreitol, failed to substitute for AA. The effect of AA was stronger when it was added during the initial 4 days during the development of mesodermal cells than when it was added during the last 4 days. On day 4 of the culture period, AA increased the total cell recovery and frequency of osteoclast precursors. Magnetic cell sorting using anti-Flk-1 antibody enriched osteoclast precursors oil day 4, and the proportion of Flk-1-positive cells but not that of platelet-derived growth factor receptor alpha-positive cells was increased by the addition of AA. These results suggest that AA might promote osteoclastogenesis of ES cells through increasing Flk-1-positive cells, which then give rise to osteoclast precursors. (c) 2005 Elsevier Inc. All rights reserved.