Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL-induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling.
Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL-induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling.
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Pectolinarigenin 可防止卵巢切除小鼠的骨质流失，并通过阻断 MAPK 和 NFATc1 信号传导的激活来抑制 RANKL 诱导的破骨细胞生成。
DOI：
10.1002/jcp.28079
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发表时间：
2019
影响因子：
5.6
通讯作者：
Xu Jiake
中科院分区：
文献类型：
--
作者：
Xiao Yu;Li Kai;Wang Ziyi;Fu Fangsheng;Shao Siyuan;Song Fangming;Zhao Jinmin;Chen Weiwei;Liu Qian;Xu Jiake
骨质疏松症(OP)是一种由多种因素引起的以单位体积骨量减少和骨微结构破坏为特征的代谢性疾病。破骨细胞功能异常是OP的主要原因，因此，调控破骨细胞的分化和功能是OP的治疗策略之一。胡萝卜素(Pectolinarigin，PEC)是从紫茎泽兰中分离得到的一种药用植物。通过抗酒石酸酸性磷酸酶染色、纤维肌动蛋白环形成和羟基磷灰石吸收实验，我们的实验数据表明，PEC能够抑制核因子-κB配体受体激活剂在体外诱导的破骨细胞生成。在机制上，PEC抑制破骨细胞生成相关基因的表达，包括组织蛋白酶K(CTSK)、基质金属蛋白酶9(MMP9)和TRACP(Acp5)。Western印迹分析表明，PEC能显著阻断RANKL诱导的丝裂原活化蛋白激酶信号转导通路，并能抑制活化T细胞核因子和c-Fos的蛋白表达。同时，PEC还以浓度依赖的方式降低细胞内的活性氧水平。此外，PEC还可预防去卵巢所致的体内骨丢失。综上所述，我们的数据提示PEC抑制破骨细胞的形成和功能以及RANKL信号通路，因此有可能用于治疗破骨细胞相关的骨丢失疾病。
Osteoporosis (OP) is a metabolic disease caused by multiple factors, which is characterized by a reduction of bone mass per unit volume and destruction of bone microstructure. Aberrant osteoclast function is the main cause of OP, therefore, regulating the differentiation and function of osteoclast is one of the treatment strategies for OP. Pectolinarigenin (PEC) is a medicinal implant isolated fromFragrant Eupatorium. Our experimental data showed that PEC was able to inhibit receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis in vitro, by tartrate‐resistant acid phosphatase (TRAcP) staining, Fibrous actin ring formation, and hydroxyapatite resorption assays. In terms of mechanism, PEC inhibited the expression of the osteoclastogenesis‐related gene, including cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and TRAcP (Acp5). Western blot analysis demonstrated that PEC could significantly block the activation of RANKL‐induced mitogen‐activated protein kinase signaling cascades and was able to suppress the protein expression of nuclear factor of activated T‐cells and c‐Fos. Meanwhile, the intracellular reactive oxygen species levels were also reduced by PEC in a concentration‐dependent manner. Further, PEC could prevent the ovariectomy‐induced bone loss in vivo. Summarizing all, our data suggested that PEC inhibits osteoclast formation and function and RANKL signaling pathways, and thus could potentially be used in the treatment the osteoclast‐related bone loss diseases.