Evidence map›Paper›PMID 34730803›Full record

ArticleRheumatology (Oxford, England)2022

Long non-coding RNA expression profiling of subchondral bone reveals AC005165.1 modifying FRZB expression during osteoarthritis.

Margo Tuerlings, Marcella van Hoolwerff, Jessica M van Bokkum, H Eka D Suchiman, Nico Lakenberg, Demiën Broekhuis, Rob G H H Nelissen, Yolande F M Ramos, Hailiang Mei, Davy Cats and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 27% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 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

12 authors at 1 institution in 1 country.

Margo TuerlingsDepartment of Biomedical Data Sciences.ORCID 0000-0002-1728-7488
Marcella van HoolwerffDepartment of Biomedical Data Sciences.
Jessica M van BokkumDepartment of Biomedical Data Sciences.
H Eka D SuchimanDepartment of Biomedical Data Sciences.
Nico LakenbergDepartment of Biomedical Data Sciences.
Demiën BroekhuisDepartment of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
Rob G H H NelissenDepartment of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
Yolande F M RamosDepartment of Biomedical Data Sciences.ORCID 0000-0003-1459-413X
Hailiang MeiDepartment of Biomedical Data Sciences.ORCID 0000-0003-1781-5508
Davy CatsDepartment of Biomedical Data Sciences.ORCID 0000-0001-9684-220X
Rodrigo Coutinho de AlmeidaDepartment of Biomedical Data Sciences.ORCID 0000-0001-7966-056X
Ingrid MeulenbeltDepartment of Biomedical Data Sciences.
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo gain insight in the expression profile of long non-coding RNAs (lncRNAs) in OA subchondral bone.

methodsRNA sequencing data of macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N = 22 pairs; 5 hips, 17 knees, Research osteoArthrits Articular Tissue (RAAK study) was run through an in-house pipeline to detect expression of lncRNAs. Differential expression analysis between preserved and lesioned bone was performed. Spearman correlations were calculated between differentially expressed lncRNAs and differentially expressed mRNAs identified previously in the same samples. Primary osteogenic cells were transfected with locked nucleic acid (LNA) GapmeRs targeting AC005165.1 lncRNA, to functionally investigate its potential mRNA targets.

resultsIn total, 2816 lncRNAs were well-expressed in subchondral bone and we identified 233 lncRNAs exclusively expressed in knee and 307 lncRNAs exclusively in hip. Differential expression analysis, using all samples (N = 22 pairs; 5 hips, 17 knees), resulted in 21 differentially expressed lncRNAs [false discovery rate (FDR) < 0.05, fold change (FC) range 1.19-7.39], including long intergenic non-protein coding RNA (LINC) 1411 (LINC01411, FC = 7.39, FDR = 2.20 × 10-8), AC005165.1 (FC = 0.44, FDR = 2.37 × 10-6) and empty spiracles homeobox 2 opposite strand RNA (EMX2OS, FC = 0.41, FDR = 7.64 × 10-3). Among the differentially expressed lncRNAs, five were also differentially expressed in articular cartilage, including AC005165.1, showing similar direction of effect. Downregulation of AC005165.1 in primary osteogenic cells resulted in consistent downregulation of highly correlated frizzled related protein (FRZB).

conclusionThe current study identified a novel lncRNA, AC005165.1, being dysregulated in OA articular cartilage and subchondral bone. Downregulation of AC005165.1 caused a decreased expression of OA risk gene FRZB, an important member of the wnt pathway, suggesting that AC005165.1 could be an attractive potential therapeutic target with effects in articular cartilage and subchondral bone.

Indexed as

Cartilage, ArticularIntracellular Signaling Peptides and ProteinsOsteoarthritisOsteoarthritis, KneeRNA, Long NoncodingBone and BonesFrizzled-Related ProteinsHumansKnee JointRNA, MessengerFrizzled-Related ProteinsIntracellular Signaling Peptides and ProteinsRNA, Long NoncodingRNA, Messengerarticular cartilagelong non-coding RNAOAsubchondral bone

Identifiers

PMID34730803
PMCPMC9258540
OpenAlexW3209134411

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.