The dietary anthocyanin delphinidin prevents bone resorption by inhibiting Rankl‐induced differentiation of osteoclasts in a medaka (Oryzias latipes) model of osteoporosis

Abstract

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‐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 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.

Maqui berry extract prevents cigarette smoke induced oxidative stress in human osteoblasts in vitro

“…It is the first time to test the effects of MBE on human bone cells in vitro , and MBE showed no obvious effect on hOBs in the absence of increased oxidative stress during osteogenic differentiation. Consistent with our results, an in vivo study reported that delphinidin had no effect on osteoblast differentiation and distribution in a fish model (Imangali et al, 2020[ 20 ]). Moreover, incubation with MBE enhanced hOB cell viability, differentiation, and matrix mineralization suppressed by CSE, suggesting MBE had a protective effect on CSE-impaired hOBs (Figure 7 (Fig.…”

Research Progress of the Role of Anthocyanins on Bone Regeneration

“…Increasing evidence has demonstrated the beneficial role of ACNs on bone health (Zheng et al, 2016;Melough et al, 2017;Shimizu et al, 2018;Speer et al, 2020). Many ACNs could promote the differentiation of mesenchymal stem cells into osteoblasts and/or inhibit osteoclastogenesis (Park et al, 2015;Dou et al, 2016;Sakaki et al, 2018;Nagaoka et al, 2019a;Nagaoka et al, 2019b;Casati et al, 2019;Saulite et al, 2019;Domazetovic et al, 2020;Hu et al, 2021;Imangali et al, 2021;Karunarathne et al, 2021). In this review, the effects of different ACNs on bone regeneration were described in detail respectively as below and summarized in Table 3.…”

Communications Between Bone Marrow Macrophages and Bone Cells in Bone Remodeling

“…Further studies found that miR-506-3p can selectively inhibit NFATc1 in RANKL-induced activated rat BMMs, further reduce the release of bone resorption enzymes, thus relieving osteolysis (Dinesh et al, 2020). What's more, both the smo-GLI1/2 axis (Hh ligands permitting the activation of Hh signal transducer smoothened (SMO) and transmitting intracellular signaling through transcription factors of the GLI family)in the Hedgehog (Hh) signaling pathway (Kohara et al, 2020) and delphinidin (Imangali et al, 2020) can mediate the regulation of osteoclasts by macrophages.…”