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首页> 外文期刊>Journal of Fish Biology >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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The dietary anthocyanin delphinidin prevents bone resorption by inhibiting Rankl-induced differentiation of osteoclasts in a medaka (Oryzias latipes) model of osteoporosis

机译:膳食花青素Delphinidin通过抑制骨髓病变中的骨髓内骨蛋白酶抑制的骨壳诱导分化来预防骨吸收

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摘要

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.
机译:花色素苷飞燕草苷是一种天然化合物,作为水溶性色素存在于有色水果和浆果中。富含花青素的饮食被认为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medaka(Oryzias latipes)骨质疏松症模型来测试delphinidin对体内骨细胞的影响。在该模型中,NF-kβ配体受体激活剂(Rankl)的可诱导转基因表达导致破骨细胞异位形成和过度骨吸收,类似于人类骨质疏松症患者的情况。在medaka骨报告细胞系中使用实时成像,我们显示delphinidin显著减少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,delphinidin主要影响巨噬细胞向破骨细胞的从头分化,而不是巨噬细胞向骨吸收部位的募集。对于已经存在的破骨细胞,delphinidin治疗会影响其形态,导致突起减少,形状更为球形。delphinidin并未增加细胞凋亡率,这表明破骨细胞数量的减少主要是由于巨噬细胞祖细胞分化受损和破骨细胞维持能力的降低。重要的是,与之前报道的细胞培养实验相比,在medaka体内未观察到delphinidin对成骨细胞分化和分布的影响。我们的研究是关于delphinidin对鱼类胚胎中骨细胞影响的首次报告,这是一种独特的复合测试模型系统,适用于活体骨细胞行为的活体成像。

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