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新橙皮苷抑制小鼠破骨细胞分化、骨吸收及去卵巢诱导的骨质疏松。

Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice.

作者信息

Tan Zhen, Cheng Jianwen, Liu Qian, Zhou Lin, Kenny Jacob, Wang Tao, Lin Xixi, Yuan Jinbo, Quinn Julian M W, Tickner Jennifer, Hong Guoju, Qin An, Zhao Jinmin, Xu Jiake

机构信息

Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.

出版信息

Mol Cell Endocrinol. 2017 Jan 5;439:369-378. doi: 10.1016/j.mce.2016.09.026. Epub 2016 Sep 21.

DOI:10.1016/j.mce.2016.09.026
PMID:27664516
Abstract

Excessive bone resorption by osteoclasts plays an important role in osteoporosis. Bone loss occurs in ovariectomised (OVX) mice in a similar manner to that in humans, so this model is suitable for evaluating potential new therapies for osteoporosis. Neohesperidin (NE) is a flavonoid compound isolated from citrus fruits. Its role in bone metabolism is unknown. In this study we found that neohesperidin inhibits osteoclast differentiation, bone resorption and the expression of osteoclast marker genes, tartrate-resistant acid phosphatase and cathepsin K. In addition, neohesperidin inhibited receptor activator of NF-κB ligand (RANKL)-induced activation of NF-κB, and the degradation of inhibitor of kappa B-alpha (IκBα). Furthermore, neohesperidin inhibited RANKL induction of nuclear factor of activated T-cells (NFAT) and calcium oscillations. In vivo treatment of ovariectomised mice with neohesperidin protected against bone loss in mice. The results suggest neohesperidin has anti-osteoclastic effects in vitro and in vivo and possesses therapeutic potential as a natural anti-catabolic treatment in osteoporosis.

摘要

破骨细胞过度的骨吸收在骨质疏松症中起重要作用。卵巢切除(OVX)小鼠的骨质流失情况与人类相似,因此该模型适用于评估骨质疏松症潜在的新疗法。新橙皮苷(NE)是一种从柑橘类水果中分离出的类黄酮化合物。其在骨代谢中的作用尚不清楚。在本研究中,我们发现新橙皮苷可抑制破骨细胞分化、骨吸收以及破骨细胞标志物基因酒石酸抗性酸性磷酸酶和组织蛋白酶K的表达。此外,新橙皮苷可抑制核因子κB受体激活剂配体(RANKL)诱导的NF-κB激活以及κB抑制蛋白α(IκBα)的降解。此外,新橙皮苷可抑制RANKL诱导的活化T细胞核因子(NFAT)和钙振荡。用新橙皮苷对去卵巢小鼠进行体内治疗可预防小鼠骨质流失。结果表明,新橙皮苷在体外和体内均具有抗破骨细胞作用,并且作为一种天然的抗分解代谢疗法在骨质疏松症治疗中具有潜在的治疗价值。

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