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Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss

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Pubmed体系：

收录情况： ◇ SCIE

作者：
He Jianbo[1,2,3] * ; Zheng Lin[4] * ; Li Xiaojuan[5] * ; Huang Furong[6] ; Hu Sitao[6] ; Chen Lei[6] ; Jiang Manya[1] ; Lin Xianfeng[4] ; Jiang Haibo[7] ; Zeng Yifan[8] ; Ye Tianshen[9] ; Lin Dingkun[2] ; Liu Qian[10,*1] ; Xu Jiake[3,*1] ; Chen Kai[6,7,*1] ;
机构： [1]Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China [2]State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China [3]School of Biomedical Sciences, The University of Western Australia, Perth 6009, Australia [4]Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou 310000, China [5]Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China [6]Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China [7]School of Molecular Sciences, The University of Western Australia, Perth 6009, Australia [8]Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China [9]Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China [10]Guangxi Key Laboratory of Regenerative Medicine, Orthopedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
出处：
DOI： 10.1016/j.jare.2023.01.003
ISSN：

关键词： Obacunone

摘要：
Osteoporosis is the most common bone disorder where the hyperactive osteoclasts represent the leading role during the pathogenesis. Targeting hyperactive osteoclasts is currently the primary therapeutic strategy. However, concerns about the long-term efficacy and side effects of current frontline treatments persist. Alternative therapeutic agents are still needed.Obacunone (OB) is a small molecule with a broad spectrum of biological activities, particularly antioxidant and anti-inflammatory effects. This study aims to examine OB's therapeutic potential on osteoporosis and explore the rudimentary mechanisms.Osteoclast formation and osteoclastic resorption assays were carried out to examine OB's inhibitory effects in vitro, followed by the in-vivo studies of OB's therapeutic effects on ovariectomy-induced osteoporotic preclinical model. To further study the underlying mechanisms, mRNA sequencing and analysis were used to investigate the changes of downstream pathways. The molecular targets of OB were predicted, and in-silico docking analysis was performed. Ligand-target binding was verified by surface plasmon resonance (SPR) assay and Western Blotting assay.The results indicated that OB suppressed the formation of osteoclast and its resorptive function in vitro. Mechanistically, OB interacts with macrophage migration inhibitory factor (MIF) which attenuates receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced signaling pathways, including reactive oxygen species (ROS), NF-κB pathway, and mitogen-activated protein kinases (MAPKs). These effects eventually caused the diminished expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. Furthermore, our data revealed that OB alleviated estrogen deficiency-induced osteoporosis by targeting MIF and thus inhibiting hyperactive osteoclasts in vivo.These results together implicated that OB may represent as a therapeutic candidate for bone disorders caused by osteoclasts, such as osteoporosis.Copyright © 2023. Production and hosting by Elsevier B.V.

基金：
This study was supported by National Natural Science Foundation of China (82002279, 81960405, 82104898), Natural Science Foundation of Guangxi Province (2018GXNSFAA050092), Natural Science Foundation of Zhejiang Province (LY20H270015), and Wenzhou Major Science and Technology Project (2018ZY015). We acknowledge the facilities and technical assistance of the Centre for Microscopy, Characterization & Analysis, The University of Western Australia. Molecular graphics and analyses performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
JCR分区：
出版当年[2021]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China [2]State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China [3]School of Biomedical Sciences, The University of Western Australia, Perth 6009, Australia
共同第一作者：
通讯作者：
通讯机构： [3]School of Biomedical Sciences, The University of Western Australia, Perth 6009, Australia [6]Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China [7]School of Molecular Sciences, The University of Western Australia, Perth 6009, Australia [10]Guangxi Key Laboratory of Regenerative Medicine, Orthopedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China [*1]Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
推荐引用方式(GB/T 7714)：
He Jianbo,Zheng Lin,Li Xiaojuan,et al.Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss[J].JOURNAL OF ADVANCED RESEARCH.2023,53:235-248.doi:10.1016/j.jare.2023.01.003.
APA：
He Jianbo,Zheng Lin,Li Xiaojuan,Huang Furong,Hu Sitao...&Chen Kai.(2023).Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss.JOURNAL OF ADVANCED RESEARCH,53,
MLA：
He Jianbo,et al."Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss".JOURNAL OF ADVANCED RESEARCH 53.(2023):235-248

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