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7-HYB,一种从厚朴中分离得到的酚类化合物,通过 BMP2 和 β-连环蛋白信号通路促进细胞迁移、成骨细胞分化和矿化。

7-HYB, a Phenolic Compound Isolated from Houtt Increases Cell Migration, Osteoblast Differentiation, and Mineralization through BMP2 and β-catenin Signaling.

机构信息

Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea.

National Institute for Korean Medicine Development, Gyeongsan 38540, Korea.

出版信息

Int J Mol Sci. 2020 Oct 29;21(21):8059. doi: 10.3390/ijms21218059.

DOI:10.3390/ijms21218059
PMID:33137925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7663243/
Abstract

The seeds (nutmegs) of Houtt have been used as popular spices and traditional medicine to treat a variety of diseases. A phenolic compound, ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene-2,4-diol (7-HYB) was isolated from the seeds of . This study aimed to investigate the anabolic effects of 7-HYB in osteogenesis and bone mineralization. In the present study, 7-HYB promotes the early and late differentiation of MC3T3-E1 preosteoblasts. 7-HYB also elevated cell migration rate during differentiation of the preosteoblasts with the increased phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2, p38, and JNK. In addition, 7-HYB induced the protein level of BMP2, the phosphorylation of Smad1/5/8, and the expression of RUNX2. 7-HYB also inhibited GSK3β and subsequently increased the level of β-catenin. However, in bone marrow macrophages (BMMs), 7-HYB has no biological effects in cell viability, TRAP-positive multinuclear osteoclasts, and gene expression (c-Fos and NF-ATc1) in receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Our findings suggest that 7-HYB plays an important role in osteoblast differentiation through the BMP2 and β-catenin signaling pathway. It also indicates that 7-HYB might have a therapeutic effect for the treatment of bone diseases such as osteoporosis and periodontitis.

摘要

药用植物荜茇的种子(肉豆蔻)被用作流行的香料和传统药物来治疗各种疾病。本研究从荜茇种子中分离得到一种酚类化合物 ((7S)-8'-(苯并[3',4']二氧杂环戊-1'-基)-7-羟丙基) 苯-2,4-二醇(7-HYB)。本研究旨在探讨 7-HYB 在成骨和骨矿化中的合成代谢作用。在本研究中,7-HYB 促进 MC3T3-E1 前成骨细胞的早期和晚期分化。7-HYB 还通过增加丝裂原活化蛋白激酶(MAPKs)包括 ERK1/2、p38 和 JNK 的磷酸化,提高前成骨细胞分化过程中的细胞迁移率。此外,7-HYB 诱导 BMP2 蛋白水平、Smad1/5/8 的磷酸化和 RUNX2 的表达。7-HYB 还抑制 GSK3β,随后增加 β-连环蛋白的水平。然而,在骨髓巨噬细胞(BMMs)中,7-HYB 对细胞活力、核因子-κB 受体激活剂配体(RANKL)诱导的破骨细胞分化中的破骨细胞中 TRAP 阳性多核和成骨细胞特异性转录因子 2(c-Fos 和 NF-ATc1)的基因表达没有生物学效应。我们的研究结果表明,7-HYB 通过 BMP2 和 β-连环蛋白信号通路在成骨细胞分化中发挥重要作用。这也表明 7-HYB 可能对骨质疏松症和牙周炎等骨疾病的治疗具有治疗作用。

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