Evidence map›Paper›PMID 34047464›Full record

ArticleClinical and translational medicine2021

A novel RANKL-targeted flavonoid glycoside prevents osteoporosis through inhibiting NFATc1 and reactive oxygen species.

Guoju Hong, Zhenqiu Chen, Xiaorui Han, Lin Zhou, Fengxiang Pang, Rishana Wu, Yingshan Shen, Xiaoming He, Zhinan Hong, Ziqi Li and 2 more

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

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  20. Application of Antioxidant Compounds in Bone Defect Repair.Antioxidants (Basel, Switzerland) · 2024
    Review
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

12 authors at 4 institutions in 3 countries.

Guoju HongDivision of Orthopaedic Surgery, The University of Alberta, Edmonton, Alberta, Canada.
Zhenqiu ChenDepartment of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Xiaorui HanDivision of Bioengineering, School of Medicine, South China University of Technology, Guangzhou, Guangdong, P.R. China.
Lin ZhouDepartment of Endocrinology, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
Fengxiang PangTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Rishana WuTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Yingshan ShenTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Xiaoming HeTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Zhinan HongTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.ORCID 0000-0003-2646-3911
Ziqi LiTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Wei HeTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Qiushi WeiTraumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.ORCID 0000-0002-1274-9997
Guangzhou University of Chinese Medicine · CNFirst Affiliated Hospital of Guangzhou University of Chinese Medicine · CNSecond Affiliated Hospital of Guangzhou Medical University · CNSouth China University of Technology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeOsteoporosis is characterized by excessive bone resorption due to enhanced osteoclast activation. Stimulation of nuclear factor of activated T cells 1 (NFATc1) and accumulation of reactive oxygen species (ROS) are important mechanisms underlying osteoclastogenesis. Robinin (Rob) is a flavonoid glycoside that has shown anti-inflammatory and antioxidative effects in previous studies, but little is known about its effects on bone homeostasis. The purpose of our research was to investigate whether Rob could prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms.

methodsThe docking pose of Rob and RANKL was identified by protein-ligand molecular docking. Rob was added to bone marrow macrophages (BMMs) stimulated by nuclear factor-κB (NF-κB) ligand (RANKL). The effects of Rob on osteoclastic activity were evaluated by positive tartrate resistant acid phosphatase (TRAcP) staining kit and hydroxyapatite resorption assay. RANKL-induced ROS generation in osteoclasts was detected by H

resultsComputational docking results showed that Rob could bind specifically to RANKL's predicted binding sites. In vitro, Rob inhibited RANKL-mediated osteoclastogenesis dose-dependently without obvious cytotoxicity at low concentrations. We also found that Rob attenuated RANKL-induced mitochondrial ROS production or enhanced activities of ROS-scavenging enzymes, and ultimately reduced intracellular ROS levels. Rob abrogated the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, and subsequently blocked NFATc1 signaling and TRAcP expression. In addition, Rob inhibited osteoclast proliferation by downregulating the expression of osteoclast target genes (Acp5, Cathepsin K, Atp6v0d2, Nfact1, c-Fos, and Mmp9) and reducing Ca

conclusionsRob inhibits the activation of osteoclasts by targeting RANKL and is therefore a potential osteoporosis drug.

Indexed as

AnimalsApoptosisCell Cycle CheckpointsFemaleFlavonoidsGlycosidesMiceNFATC Transcription FactorsOsteoclastsOsteoporosisOvariectomyProtein BindingRANK LigandReactive Oxygen SpeciesFlavonoidsGlycosidesNfatc1 protein, mouseNFATC Transcription FactorsRANK LigandReactive Oxygen SpeciesTnfsf11 protein, mouseNFAcT1osteoclastosteoporosisRANKLRobininROS

Identifiers

PMID34047464
PMCPMC8140192
OpenAlexW3165560299

What OpenQuestion holds

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Registered trials

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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.