Hagiwara Hiromi, Nakata Kyoko, Miyazaki Hitoshi, Maehashi Sanae, Komiyama Yuki, Aida Rieko, Yoshida Shigeki, Kokubu Daichi, Hagiwara Keitaro, Yoshida Kaoru
Faculty of Biomedical Engineering, Toin University of Yokohama, 1614 Kurogane-cho, Aoba-ku, Yokohama, 225-8503, Japan.
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8572, Japan.
Cytotechnology. 2019 Feb;71(1):15-22. doi: 10.1007/s10616-018-0236-2. Epub 2018 Nov 24.
4-Hydroxyderricin (4-HD) is a major polyphenol of Angelica keiskei (Japanese name Ashitaba), exhibiting anti-allergic, anti-diabetic, anti-oxidant, and antitumor effects. The present study was designed to evaluate the effects of 4-HD on bone formation and maintenance by using cultured osteoclasts and osteoblasts. 4-HD did not affect cell proliferation of stromal ST2 cells and preosteoblast MC3T3-E1 cells at concentrations of 1-10 μM. This compound inhibited the formation of multinucleated osteoclasts from mouse splenic cells, and we identified a molecular pathway of osteoclast differentiation mediated by 4-HD, which led to inhibition of the expression of receptor activator of nuclear factor-κB ligand and macrophage-colony stimulating factor in ST2 cells. By contrast, 4-HD enhanced indices of osteoblast differentiation, such as alkaline phosphatase activity and calcium deposition by osteoblastic MC3T3-E1 cells, at concentrations of 1-10 μM. Furthermore, we found that 4-HD at 1 μM attenuated HO levels in MC3T3-E1 cells. Our findings indicate that 4-HD may have critical effects on bone formation and maintenance.
4-羟基德瑞辛（4-HD）是明日叶（日语名：アシタバ）中的一种主要多酚，具有抗过敏、抗糖尿病、抗氧化和抗肿瘤作用。本研究旨在通过培养破骨细胞和成骨细胞来评估4-HD对骨形成和维持的影响。在1-10 μM浓度下，4-HD对基质ST2细胞和前成骨细胞MC3T3-E1细胞的细胞增殖没有影响。该化合物抑制了小鼠脾细胞中多核破骨细胞的形成，并且我们确定了一条由4-HD介导的破骨细胞分化分子途径，该途径导致ST2细胞中核因子κB受体活化因子配体和巨噬细胞集落刺激因子的表达受到抑制。相比之下，在1-10 μM浓度下，4-HD增强了成骨细胞分化指标，如碱性磷酸酶活性和成骨细胞MC3T3-E1细胞的钙沉积。此外，我们发现1 μM的4-HD可降低MC3T3-E1细胞中的活性氧水平。我们的研究结果表明，4-HD可能对骨形成和维持具有关键作用。
