Zhang Fangxue, Huang Xiaowei, Qi Yuhan, Qian Zhi, Ni Shuo, Zhong Zeyuan, Zhang Xu, Li Dejian, Yu Baoqing
Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
Front Pharmacol. 2021 Jan 27;11:596230. doi: 10.3389/fphar.2020.596230. eCollection 2020.
Bone metabolism is a physiological process that involves both osteoblasts and osteoclasts. Pathological changes of osteoclasts are commonly seen in osteoporosis diseases. Juglanin is a natural compound, reported to have an inhibitory effect on inflammation, oxidative stress and cancer progression. The purpose of this study is to explore the role that Juglanin plays on the osteoclast functions and underlying signaling pathways. study demonstrated that Juglanin had negative influence on osteoclastic differentiation by suppressing the transcription activity of osteoclastogenesis-related genes and proteins. To determine the underlying mechanism, Western blot was employed to show that Juglanin could significantly have negative effect on the phosphorylation of P50, P65, I-κB, ultimately suppressing the expression and transcriptional activity of nuclear factor of activated T cells (NFATc1). Juglanin treatment attenuate bone reducing in mice with removed ovary through suppressing osteoclast functioning. Taken together, our study demonstrated that in the molecular mechanism, JUG inhibited the expression of receptor activator of nuclear factor-κ B ligand (RANKL) induced NF - B signaling pathway, thus may play a vital part in preventing postmenopausal osteoporosis.
骨代谢是一个涉及成骨细胞和破骨细胞的生理过程。破骨细胞的病理变化在骨质疏松症中很常见。胡桃素是一种天然化合物,据报道对炎症、氧化应激和癌症进展具有抑制作用。本研究的目的是探讨胡桃素在破骨细胞功能及相关信号通路中所起的作用。研究表明,胡桃素通过抑制破骨细胞生成相关基因和蛋白质的转录活性,对破骨细胞分化产生负面影响。为确定其潜在机制,采用蛋白质印迹法显示胡桃素可显著抑制P50、P65、I-κB的磷酸化,最终抑制活化T细胞核因子(NFATc1)的表达和转录活性。胡桃素治疗通过抑制破骨细胞功能减轻去卵巢小鼠的骨质流失。综上所述,我们的研究表明,在分子机制上,胡桃素抑制核因子-κB受体活化因子配体(RANKL)诱导的NF-κB信号通路的表达,因此可能在预防绝经后骨质疏松症中发挥重要作用。