The identification of hub-methylated differentially expressed genes in osteoarthritis patients is based on epigenomic and transcriptomic data.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37465641", "kind": "science-record", "revision": 2, "content_hash": "sha256:50a9a06bf6c49f9680d38272b25958e30861f85d67a71a9eea7a93dac73f95ae", "created_at": "2026-11-01T19:02:14Z", "updated_at": "2026-11-01T21:31:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The identification of hub-methylated differentially expressed genes in osteoarthritis patients is based on epigenomic and transcriptomic data.", "doi": "10.3389/fmed.2023.1219830", "pmid": "37465641", "authors": ["Zhen-Chen Chu", "Ting Cong", "Jian-Yu Zhao", "Jian Zhang", "Zhi-Yuan Lou", "Yang Gao", "Xin Tang"], "journal": "Frontiers in medicine", "year": 2023, "abstract": "Introduction: Osteoarthritis (OA) refers to a commonly seen degenerative joint disorder and a major global public health burden. According to the existing literature, osteoarthritis is related to epigenetic changes, which are important for diagnosing and treating the disease early. Through early targeted treatment, costly treatments and poor prognosis caused by advanced osteoarthritis can be avoided.\nMethods: This study combined gene differential expression analysis and weighted gene co-expression network analysis (WGCNA) of the transcriptome with epigenome microarray data to discover the hub gene of OA. We obtained 2 microarray datasets (GSE114007, GSE73626) in Gene Expression Omnibus (GEO). The R software was utilized for identifying differentially expressed genes (DEGs) and differentially methylated genes (DMGs). By using WGCNA to analyze the relationships between modules and phenotypes, it was discovered that the blue module (MEBlue) has the strongest phenotypic connection with OA (cor = 0.92, p = 4e-16). The hub genes for OA, also known as the hub methylated differentially expressed genes, were identified by matching the MEblue module to differentially methylated differentially expressed genes. Furthermore, this study used Gene set variation analysis (GSVA) to identify specific signal pathways associated with hub genes. qRT-PCR and western blotting assays were used to confirm the expression levels of the hub genes in OA patients and healthy controls.\nResults: Three hub genes were discovered: HTRA1, P2RY6, and RCAN1. GSVA analysis showed that high HTRA1 expression was mainly enriched in epithelial-mesenchymal transition and apical junction; high expression of P2RY6 was mainly enriched in the peroxisome, coagulation, and epithelial-mesenchymal transition; and high expression of RCAN1 was mainly enriched in epithelial-mesenchymal-transition, TGF-β-signaling, and glycolysis. The results of the RT-qPCR and WB assay were consistent with the findings.\nDiscussion: The three genes tested may cause articular cartilage degeneration by inducing chondrocyte hypertrophy, regulating extracellular matrix accumulation, and improving macrophage pro-inflammatory response, resulting in the onset and progression of osteoarthritis. They can provide new ideas for targeted treatment of osteoarthritis.", "claims": [{"id": "claim-method", "statement": "This study combined gene differential expression analysis and weighted gene co-expression network analysis (WGCNA) of the transcriptome with epigenome microarray data to discover the hub gene of OA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37465641", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "This study combined gene differential expression analysis and weighted gene co-expression network analysis (WGCNA) of the transcriptome with epigenome microarray data to discover the hub gene of OA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37465641", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three OA-related hub genes—HTRA1, P2RY6, and RCAN1—were identified by intersecting WGCNA blue-module genes with differentially methylated differentially expressed genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37465641", "locator": "sections[16] \"3.3. Identification of hub genes for OA\" paragraph 2", "quote": "Three hub genes for OA (HTRA1, HtrA serine peptidase 1; P2RY6, pyrimidinergic receptor P2Y6 and RCAN1, regulator of calcineurin 1) were identified by intersecting WGCNA blue module genes with differentially methylated differentially expressed genes (Figure 5)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Three OA-related hub genes—HTRA1, P2RY6, and RCAN1—were identified by intersecting WGCNA blue-module genes with differentially methylated differentially expressed genes.", "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:37465641"], "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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