Evidence map›Paper›PMID 36657717›Full record

ArticleJournal of advanced research2023

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

Jianbo He, Lin Zheng, Xiaojuan Li, Furong Huang, Sitao Hu, Lei Chen, Manya Jiang, Xianfeng Lin, Haibo Jiang, Yifan Zeng and 5 more

Open access · goldAbstract read
In one paragraph

Article in Journal of advanced research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Jianbo HeGuangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China; 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; School of Biomedical Sciences, The University of Western Australia, Perth 6009, Australia.
Lin ZhengDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou 310000, China.
Xiaojuan LiFormula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.
Furong HuangDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Sitao HuDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Lei ChenDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Manya JiangGuangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China.
Xianfeng LinDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou 310000, China.
Haibo JiangSchool of Molecular Sciences, The University of Western Australia, Perth 6009, Australia.
Yifan ZengDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Tianshen YeDepartment of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Dingkun LinState 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.
Qian LiuGuangxi Key Laboratory of Regenerative Medicine, Orthopedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: liuqian@gxmu.edu.cn.
Jiake XuSchool of Biomedical Sciences, The University of Western Australia, Perth 6009, Australia. Electronic address: jiake.xu@uwa.edu.au.
Kai ChenDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; School of Molecular Sciences, The University of Western Australia, Perth 6009, Australia. Electronic address: kai.chen@uwa.edu.au.
Wenzhou Medical University · CNThe University of Western Australia · AUGuangzhou University of Chinese Medicine · CNJinan University · CNSir Run Run Shaw Hospital · CNGuangxi Medical University · CN

Funding

Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
NIGMS NIH HHS P41 GM103311
6 · The paper itself

Abstract

introductionOsteoporosis 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.

objectivesObacunone (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.

methodsOsteoclast 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.

resultsThe 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.

conclusionThese results together implicated that OB may represent as a therapeutic candidate for bone disorders caused by osteoclasts, such as osteoporosis.

Indexed as

Macrophage Migration-Inhibitory FactorsOsteoporosisBenzoxepinsFemaleHumansIntramolecular OxidoreductasesLigandsLimoninsNF-kappa BOsteogenesisOvariectomyBenzoxepinsIntramolecular OxidoreductasesLigandsLimoninsMacrophage Migration-Inhibitory FactorsMIF protein, humanNF-kappa BobacunoneBone lossMacrophage migration inhibitory factor (MIF)ObacunoneOsteoclastReactive oxygen species (ROS)

Identifiers

PMID36657717
PMCPMC10658311
OpenAlexW4316506391

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.