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pmid:33936160

Analysis of mRNA Expression and DNA Methylation Datasets According to the Genomic Distribution of CpG Sites in Osteoarthritis.

Peng Yi · Xiongfeng Xu · Jiawei Yao · Bo Qiu

Frontiers in genetics · 2021 doi:10.3389/fgene.2021.618803

Paper

complete

Experiment

complete

Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33936160
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science-record
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2026-11-01T15:41:34Z
updated_at
2026-11-01T22:03:40Z
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paper object · 10 fields
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title
Analysis of mRNA Expression and DNA Methylation Datasets According to the Genomic Distribution of CpG Sites in Osteoarthritis.
doi
10.3389/fgene.2021.618803
pmid
33936160
authors array · 4 items
[0]
Peng Yi
[1]
Xiongfeng Xu
[2]
Jiawei Yao
[3]
Bo Qiu
journal
Frontiers in genetics
year
2021
abstract
Objectives Transcriptional changes in cartilage can impact function by causing degradation such as that which occurs during the development of osteoarthritis (OA). Epigenetic regulation may be a key factor leading to transcriptional changes in OA. In this study, we performed a combined analysis of DNA methylation and gene expression microarray datasets and identified key transcription factors (TFs) central to the regulation of gene expression in OA. Methods A DNA methylation profile dataset (GSE63106) and a gene expression profiling dataset (GSE114007) were extracted from the Gene Expression Omnibus (GEO). We used ChAMP methylation analysis and the Limma package to identify differentially methylation genes (DMGs) and differentially expressed genes (DEGs) from normal and human knee cartilage samples in OA. Function enrichment analysis of DMGs was conducted using the DAVID database. A combined analysis of DEGs and DMGs was conducted to identify key TFs in OA. We then validated the mRNA expression of selected TFs in normal and OA cartilage by RT-qPCR. Primary chondrocytes were cultured and treated with the DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza) for functional validation. Results We identified 2,170 differential methylation sites (DMS) containing 1005 genes and 1986 DEGs between normal human and OA cartilage. Functional analysis of DMGs revealed that focal adhesion, extracellular matrix (ECM)-receptor interactions, the PI3K-Akt signaling pathway, and the FoxO signaling pathway were involved in OA. Integrated analysis showed a subset of 17 TFs. Four TFs (ELF3, SOX11, RARA, and FOXD2) were validated. RT-qPCR results showed the mRNA expression of SOX11, RARA, and FOXD2 were consistent with the results from the mRNA expression data. However, the expression of ELF3 could not be validated. Upon 5-Aza-2'-deoxycytidine (5-Aza) treatment, the mRNA levels of ELF3 and SOX11 were down-regulated, whilst RARA was up-regulated, and FOXD2 showed no significant change in expression level. Conclusions the effect of DNA methylation on the transcriptional regulation is related to the distribution of methylated sites across the genome. Epigenetic studies on the positions of DMS in transcriptional units can inform a better understanding of the function of DNA methylation and its transcription regulation.
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GSE63106 was used to collect data from the preserved and affected cartilage samples obtained from 17 knees and 14 hip joints undergoing joint replacement surgery due to primary OA.
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Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis
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Assessing transcriptionally functional CpGs in articular cartilage
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CACACACCTGAGCAGCATCAC
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Statistical Analysis of CpG Sites
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DMS and Array sites (after filtering) in different genomic regions.
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DMS
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DETFs harboring DMS in knee articular cartilage from normal and OA patients.
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Integrative Analysis of DNA Methylation and Gene Expression
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1.303540248
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f selected TFs in normal and OA cartilage by RT-qPCR. Primary chondrocytes were cultured and trea
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33936160", "kind": "science-record", "revision": 8, "content_hash": "sha256:ec392c0ac549142c0d7c7f3ae6538a735921f99a322403b20747daa22529422b", "created_at": "2026-11-01T15:41:34Z", "updated_at": "2026-11-01T22:03:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of mRNA Expression and DNA Methylation Datasets According to the Genomic Distribution of CpG Sites in Osteoarthritis.", "doi": "10.3389/fgene.2021.618803", "pmid": "33936160", "authors": ["Peng Yi", "Xiongfeng Xu", "Jiawei Yao", "Bo Qiu"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Objectives Transcriptional changes in cartilage can impact function by causing degradation such as that which occurs during the development of osteoarthritis (OA). Epigenetic regulation may be a key factor leading to transcriptional changes in OA. In this study, we performed a combined analysis of DNA methylation and gene expression microarray datasets and identified key transcription factors (TFs) central to the regulation of gene expression in OA. Methods A DNA methylation profile dataset (GSE63106) and a gene expression profiling dataset (GSE114007) were extracted from the Gene Expression Omnibus (GEO). We used ChAMP methylation analysis and the Limma package to identify differentially methylation genes (DMGs) and differentially expressed genes (DEGs) from normal and human knee cartilage samples in OA. Function enrichment analysis of DMGs was conducted using the DAVID database. A combined analysis of DEGs and DMGs was conducted to identify key TFs in OA. We then validated the mRNA expression of selected TFs in normal and OA cartilage by RT-qPCR. Primary chondrocytes were cultured and treated with the DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza) for functional validation. Results We identified 2,170 differential methylation sites (DMS) containing 1005 genes and 1986 DEGs between normal human and OA cartilage. Functional analysis of DMGs revealed that focal adhesion, extracellular matrix (ECM)-receptor interactions, the PI3K-Akt signaling pathway, and the FoxO signaling pathway were involved in OA. Integrated analysis showed a subset of 17 TFs. Four TFs (ELF3, SOX11, RARA, and FOXD2) were validated. RT-qPCR results showed the mRNA expression of SOX11, RARA, and FOXD2 were consistent with the results from the mRNA expression data. However, the expression of ELF3 could not be validated. Upon 5-Aza-2'-deoxycytidine (5-Aza) treatment, the mRNA levels of ELF3 and SOX11 were down-regulated, whilst RARA was up-regulated, and FOXD2 showed no significant change in expression level. Conclusions the effect of DNA methylation on the transcriptional regulation is related to the distribution of methylated sites across the genome. Epigenetic studies on the positions of DMS in transcriptional units can inform a better understanding of the function of DNA methylation and its transcription regulation.", "claims": [{"id": "claim-method", "statement": "Data between the two groups were compared using an unpaired Student’s t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33936160", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "Data between the two groups were compared using an unpaired Student’s t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE63106 was used to collect data from the preserved and affected cartilage samples obtained from 17 knees and 14 hip joints undergoing joint replacement surgery due to primary OA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33936160", "locator": "sections[4] \"DNA Methylation Profiling and Gene Expression Data\" paragraph 2", "quote": "GSE63106 was used to collect data from the preserved and affected cartilage samples obtained from 17 knees and 14 hip joints undergoing joint replacement surgery due to primary OA."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33936160"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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