The dietary anthocyanin delphinidin prevents bone resorption by inhibiting Rankl-induced differentiation of osteoclasts in a medaka (Oryzias latipes) model of osteoporosis
The dietary anthocyanin delphinidin prevents bone resorption by inhibiting Rankl-induced differentiation of osteoclasts in a medaka (Oryzias latipes) model of osteoporosis
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DOI：
10.1111/jfb.14317
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发表时间：
2020-04-03
影响因子：
2
通讯作者：
Winkler, Christoph
中科院分区：
文献类型：
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作者：
Imangali, Nurgul;Quang Tien Phan;Winkler, Christoph
花色素苷飞燕草色素是一种天然化合物，在有色水果和浆果中发现为水溶性色素。富含花青素的饮食已被提出对人类和小鼠具有骨骼保护作用，但其潜在机制仍不清楚。在这项研究中，我们使用青鳉（Oryzias latipes）骨质疏松模型，以测试在体内的飞燕草素对骨细胞的影响。在该模型中，NF-κ β配体的受体-激活剂（Rankl）的可诱导转基因表达导致破骨细胞的异位形成和过度的骨吸收，类似于人骨质疏松症患者中的情况。在青鳉骨报告细胞系中使用实时成像，我们表明飞燕草素显著减少了Rankl诱导后破骨细胞的数量，并以剂量依赖性方式保护骨完整性。我们在体内的研究结果表明，飞燕草素主要影响从头分化的巨噬细胞成破骨细胞，而不是招募巨噬细胞的骨吸收的网站。对于已经存在的破骨细胞，飞燕草素处理影响了它们的形态，导致更少的突起和更球形的形状。凋亡率没有增加飞燕草素，这表明破骨细胞数量减少，主要是从巨噬细胞祖细胞分化受损，并减少维护预先存在的破骨细胞。重要的是，与以前报道的细胞培养实验相反，在青鳉体内没有观察到飞燕草素对成骨细胞分化和分布的影响。我们的研究是关于飞燕草素对鱼胚胎中骨细胞的影响的第一份报告，这是一个独特的模型系统，用于化合物测试，适用于体内骨细胞行为的实时成像。
The anthocyanin delphinidin is a natural compound found as water-soluble pigment in coloured fruits and berries. Anthocyanin-rich diets have been proposed to have bone protective effects in humans and mice, but the underlying mechanisms remain unclear. In this study, we used a medaka (Oryzias latipes) osteoporosis model to test the effects of delphinidin on bone cells in vivo. In this model, inducible transgenic expression of receptor-activator of NF-k beta ligand (Rankl) leads to ectopic formation of osteoclasts and excessive bone resorption, similar to the situation in human osteoporosis patients. Using live imaging in medaka bone reporter lines, we show that delphinidin significantly reduces the number of osteoclasts after Rankl induction and protects bone integrity in a dose-dependent manner. Our in vivo findings suggest that delphinidin primarily affects the de novo differentiation of macrophages into osteoclasts rather than the recruitment of macrophages to sites of bone resorption. For already existing osteoclasts, delphinidin treatment affected their morphology, leading to fewer protrusions and a more spherical shape. Apoptosis rates were not increased by delphinidin, suggesting that osteoclast numbers were reduced primarily by impaired differentiation from macrophage progenitors and reduced maintenance of pre-existing osteoclasts. Importantly, and in contrast to previously reported cell culture experiments, no effect of delphinidin on osteoblast differentiation and distribution was observed in medaka in vivo. Our study is the first report on the effects of delphinidin on bone cells in fish embryos, which are a unique model system for compound testing that is suitable for live imaging of bone cell behaviour in vivo.