Quercetin suppresses bone resorption by inhibiting the differentiation and activation of osteoclasts
Quercetin suppresses bone resorption by inhibiting the differentiation and activation of osteoclasts
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DOI：
10.1248/bpb.27.504
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发表时间：
2004-04-01
影响因子：
2
通讯作者：
Nagai, K
中科院分区：
文献类型：
--
作者：
Woo, JT;Nakagawa, H;Nagai, K
虽然在一些动物研究中，槲皮素具有抑制骨吸收的作用，但其靶细胞及其与骨吸收相关的作用机制尚未完全阐明。我们研究了槲皮素对破骨细胞分化和激活的影响。我们使用了小鼠脾细胞和ST2细胞的共培养，以及破骨细胞前体细胞的培养(小鼠骨髓的M-CSF依赖(MD)细胞和小鼠单核细胞RAW 264(RAW)细胞)。在共培养和MD细胞培养中，2-5um浓度的槲皮素均呈剂量依赖性抑制破骨细胞样(OCL)细胞的形成。在MD和生细胞培养中，栎素均能抑制核因子-kappaB受体激活剂配体(RANKL)诱导的单核破骨前细胞(POCs)抗酒石酸酸性磷酸酶(TRAP)活性的升高。槲皮素可逆地诱导OCL中肌动蛋白环的断裂。在小鼠长骨培养中，栎素还抑制破骨细胞在牙本质切片上诱导的凹坑形成，以及PTH刺激的小鼠长骨培养中钙-45的释放。这些结果表明，破骨细胞前体细胞和成熟破骨细胞都是槲皮素与骨吸收相关的靶细胞，而槲皮素对骨吸收的抑制作用是通过抑制破骨细胞前体细胞分化为POCs和破坏成熟破骨细胞中的肌动蛋白环来实现的。
Although quercetin has suppressed bone resorption in several animal studies, its target cells and the mechanism of its action related to bone resorption has not been fully elucidated. We investigated the effect of quercetin on the differentiation and activation of osteoclasts. We used cocultures of mouse spleen cells and ST2 cells, and cultures of osteoclast progenitor cells {M-CSF-dependent (MD) cells from mouse bone marrow and murine monocytic RAW 264 (RAW) cells}. Quercetin dose-dependently inhibited osteoclast-like (OCL) cell formation at 2-5 muM concentration in both the coculture and MD cell culture. Quercetin inhibited the increase of tartrate-resistant acid phosphatase (TRAP) activity of mononuclear preosteoclasts (pOCs) induced by receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) in both MD and RAW cell cultures. Quercetin reversely induced the disruption of actin rings in OCLs. Quercetin also suppressed both pit formation induced by osteoclasts on dentine slices and PTH-stimulated Ca-45 release in mouse long bone cultures. These results suggest that osteoclast progenitors as well as mature osteoclasts, are quercetin's target cells in relation to bone resorption, and that quercetin's suppressive effect on bone resorption results from both its inhibitory effect on the differentiation of osteoclast progenitor cells into pOCs and from its disruptive effect on actin rings in mature osteoclasts.