Evidence map›Paper›PMID 33692439›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2021

EZH2 is associated with cartilage degeneration in osteoarthritis by promoting SDC1 expression via histone methylation of the microRNA-138 promoter.

Jian Wang, Xiang Wang, Xu Ding, Tao Huang, Dengxin Song, Hairong Tao

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 23% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Epigenetics as a Therapeutic Target in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  14. Article
  15. Review
  16. Article
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

6 authors at 6 institutions in 1 country.

Jian WangDepartment of Orthopedics, Zhongshan Hospital Wusong Branch, Fudan University, 200940, Shanghai, PR China.
Xiang WangShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, PR China.
Xu DingDepartment of Orthopedics, Zhongshan Hospital Wusong Branch, Fudan University, 200940, Shanghai, PR China.
Tao HuangDepartment of Orthopedics, Zhongshan Hospital Wusong Branch, Fudan University, 200940, Shanghai, PR China.
Dengxin SongDepartment of Orthopedics, Zhongshan Hospital Wusong Branch, Fudan University, 200940, Shanghai, PR China.
Hairong TaoShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, PR China. taohair@163.com.
Fudan University · CNShanghai Jiao Tong University · CNShanghai Ninth People's Hospital · CNSun Yat-sen University · CNThe First Affiliated Hospital, Sun Yat-sen University · CNZhongshan Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cartilage degeneration has been reported to deteriorate osteoarthritis (OA), a prevalent joint disease caused by intrinsic and epigenetic factors. This study aimed to examine the molecular mechanism of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)/microRNA-138 (miR-138)/syndecan 1 (SDC1) and its epigenetic regulation in cartilage degeneration in OA. An OA cell model was induced by stimulating chondrocytes with interleukin (IL)-1β at a final concentration of 10 ng/mL, followed by alterations in EZH2 and miR-138 expression. Afterwards, cell apoptosis was analyzed using flow cytometry. The expression patterns of cartilage catabolism-related factors (MMP-13, ADAMTS-4, and ADAMTS-5) were determined using RT-qPCR and western blot analyses. The EZH2 and H3K27me3 enrichment at the miR-138 promoter region were determined using ChIP-qPCR. Finally, an OA mouse model was constructed to verify the function of EZH2 in vivo. EZH2 was expressed at high levels in OA models. EZH2 depletion ameliorated OA, as evidenced by reduced cell apoptosis in IL-1β-treated chondrocytes and decreased levels of cartilage catabolism-related factors. Moreover, EZH2 promoted histone methylation at the miR-138 promoter to suppress miR-138 expression, thereby upregulating the expression of SDC1, a target gene of miR-138. Changes in this pathway increased the expression of cartilage catabolism-related factors in vitro while promoting cartilage degeneration in vivo. Our data provided evidence that EZH2 inhibits miR-138 expression by promoting the histone methylation of its promoter, which induces cartilage degeneration in OA models by upregulating SDC1 expression, suggesting a novel mechanistic strategy for OA treatment.

Indexed as

AdultAnimalsArthritis, ExperimentalBiomarkersCartilage, ArticularEnhancer of Zeste Homolog 2 ProteinFemaleHistone MethyltransferasesHumansMaleMiceMicroRNAsMiddle AgedOsteoarthritisPrimary Cell CultureSyndecan-1BiomarkersEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistone MethyltransferasesMicroRNAsMIRN138 microRNA, humanSDC1 protein, humanSyndecan-1

Identifiers

PMID33692439
OpenAlexW3134549401

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.