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山奈酚通过下调 MAPKs、c-Fos 和 NFATc1 抑制 IL-1β 刺激的 RANKL 介导的破骨细胞生成。

Kaempferol inhibits IL-1β-stimulated, RANKL-mediated osteoclastogenesis via downregulation of MAPKs, c-Fos, and NFATc1.

机构信息

Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital-Chonbuk National University, 561-180, Jeonbuk, Jeonju, Republic of Korea.

出版信息

Inflammation. 2014 Aug;37(4):1221-30. doi: 10.1007/s10753-014-9849-6.

DOI:10.1007/s10753-014-9849-6
PMID:24696323
Abstract

Kaempferol is one of the most common flavonoid that is present in a variety of vegetables and fruits and has effects on bone metabolism. The present study was performed to define the effects of kaempferol on interleukin (IL)-1β-stimulated receptor activator of NF-κB ligand (RANKL)-mediated osteoclast differentiation. Bone marrow cells were harvested from 6-week-old male imprinting control region mice, and the differentiation of osteoclasts from these cells was evaluated by tartrate-resistant acid phosphatase staining and resorption pit formation assay. Phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated p38, phosphorylated c-Jun amino-terminal kinase, NF-κB (p65), IκBα, c-Fos, and nuclear factor of activated T cells c1 (NFATc1) expressions were examined by Western blotting and quantitative RT-PCR. Kaempferol inhibits IL-1β-stimulated, RANKL-mediated osteoclast differentiation and also inhibits IL-1β-stimulated, RANKL-mediated phosphorylation of ERK 1/2, p38 and JNK MAP kinases, and expressions of c-Fos and NFATc1. These results indicate that kaempferol has an inhibitory role in the bone loss by preventing osteoclast formation and suggest that it might be a novel therapeutic agent for the treatment of inflammatory arthritis by managing bone destruction.

摘要

山奈酚是一种最常见的类黄酮,存在于各种蔬菜和水果中,对骨代谢有影响。本研究旨在定义山奈酚对白细胞介素 (IL)-1β刺激核因子-κB 配体 (RANKL) 介导的破骨细胞分化的影响。从 6 周龄雄性印迹控制区小鼠中采集骨髓细胞,通过抗酒石酸酸性磷酸酶染色和吸收陷窝形成试验评估这些细胞的破骨细胞分化。通过 Western blot 和定量 RT-PCR 检测磷酸化细胞外信号调节激酶 (p-ERK)、磷酸化 p38、磷酸化 c-Jun 氨基末端激酶、NF-κB(p65)、IκBα、c-Fos 和激活 T 细胞核因子 c1 (NFATc1) 的表达。山奈酚抑制 IL-1β 刺激的 RANKL 介导的破骨细胞分化,也抑制 IL-1β 刺激的 RANKL 介导的 ERK 1/2、p38 和 JNK MAP 激酶的磷酸化以及 c-Fos 和 NFATc1 的表达。这些结果表明,山奈酚通过防止破骨细胞形成在骨丢失中起抑制作用,并表明它可能是通过管理骨破坏来治疗炎症性关节炎的新型治疗剂。

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