The anthocyanin delphinidin is a natural compound found as water-soluble pigment in coloured fruits and berries. Anthocyanin-rich diets have earlier 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-kβ 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 less 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. This article is protected by copyright. All rights reserved.

中文翻译：

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膳食花青素翠雀素通过抑制 Rankl 诱导的骨质疏松症模型中的破骨细胞分化来防止骨吸收

花青素飞燕草素是一种天然化合物，在有色水果和浆果中作为水溶性色素被发现。早先有人提出富含花青素的饮食对人类和小鼠具有骨骼保护作用，但其潜在机制尚不清楚。在这项研究中，我们使用青鳉（Oryzias latipes）骨质疏松症模型来测试飞燕草素对体内骨细胞的影响。在该模型中，NF-kβ 配体受体激活剂 (Rank1) 的诱导型转基因表达导致破骨细胞的异位形成和过度的骨吸收，类似于人类骨质疏松症患者的情况。在青鳉骨报告系中使用实时成像，我们表明花翠素显着减少了 Rankl 诱导后的破骨细胞数量，并以剂量​​依赖性方式保护骨完整性。我们的体内研究结果表明，飞燕草素主要影响巨噬细胞从头分化为破骨细胞，而不是将巨噬细胞募集到骨吸收部位。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，导致突起更少，形状更球形。飞燕草素没有增加细胞凋亡率，这表明破骨细胞数量减少主要是由于巨噬细胞祖细胞的分化受损和预先存在的破骨细胞的维持减少。重要的是，与之前报道的细胞培养实验相反，在体内 medaka 中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骨细胞影响的第一份报告，这是一种独特的化合物测试模型系统，适用于体内骨细胞行为的实时成像。本文受版权保护。版权所有。