来自石莼 okamurae 的二氢愈创木酸通过下调 NF-κB 信号通路抑制破骨细胞分化。

Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway.

机构信息

Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Biotooth Regeneration, Kyungpook National University, Daegu 41940, Korea.

Department of Marine Life Science, Jeju National University, Jeju 63243, Korea.

出版信息

Int J Mol Sci. 2017 Dec 6;18(12):2635. doi: 10.3390/ijms18122635.

DOI:10.3390/ijms18122635

PMID:29211036

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5751238/

Abstract

Marine algae possess a variety of beneficial effects on human health. In this study, we investigated whether diphlorethohydroxycarmalol (DPHC), isolated from , a brown alga, suppresses receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. DPHC significantly suppressed RANKL-induced osteoclast differentiation and macrophage-colony stimulating factor (M-CSF) expression in a dose-dependent manner. In addition, it significantly inhibited actin ring formation, the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp), and osteoclast-induced bone resorption. Analysis of the RANKL-mediated signaling pathway showed that the phosphorylation of both IκB and p65 was specifically inhibited by DPHC. These results suggest that DPHC substantially suppresses osteoclastogenesis by downregulating the RANK-NF-κB signaling pathway. Thus, it holds significant potential for the treatment of skeletal diseases associated with an enhanced osteoclast activity.

摘要

海洋藻类对人类健康具有多种有益作用。在这项研究中，我们研究了是否从褐藻中分离得到的二苯并[a,e]环庚并[1,2-b]菲-1,7,12-三醇（DPHC）能够抑制核因子-κB 受体激活剂配体（RANKL）诱导的破骨细胞分化。DPHC 能够显著抑制 RANKL 诱导的破骨细胞分化和巨噬细胞集落刺激因子（M-CSF）表达，并呈剂量依赖性。此外，它还显著抑制肌动蛋白环形成、破骨细胞标记基因如抗酒石酸酸性磷酸酶（TRAP）、激活 T 细胞核因子细胞质 1（Nfatc1）、组织蛋白酶 K（Ctsk）和树突状细胞特异性跨膜蛋白（Dcstamp）的表达，以及破骨细胞诱导的骨吸收。对 RANKL 介导的信号通路的分析表明，DPHC 特异性抑制 IκB 和 p65 的磷酸化。这些结果表明，DPHC 通过下调 RANK-NF-κB 信号通路，显著抑制破骨细胞生成。因此，它具有治疗与破骨细胞活性增强相关的骨骼疾病的巨大潜力。