Targeting the senescence-related genes MAPK12 and FOS to alleviate osteoarthritis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39007035", "kind": "science-record", "revision": 4, "content_hash": "sha256:a3bd4cdf37aeae341d2ac7b1dab2d8541ec4867150ef805a4170a1f23be363d6", "created_at": "2026-11-01T20:29:04Z", "updated_at": "2026-11-01T22:54:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Targeting the senescence-related genes MAPK12 and FOS to alleviate osteoarthritis.", "doi": "10.1016/j.jot.2024.06.008", "pmid": "39007035", "authors": ["Nana Geng", "Menglin Xian", "Lin Deng", "Biao Kuang", "Yiming Pan", "Kaiwen Liu", "Yuanlan Ye", "Mengtian Fan", "Zhixun Bai", "Fengjin Guo"], "journal": "Journal of orthopaedic translation", "year": 2024, "abstract": "Background: The mechanism by which chondrocyte senescence aggravate OA progression has not yet been well elucidated. The aim of this study was to investigate the chondrocyte senescence related gene biosignatures in OA, and to analyze on the underlying mechanisms of senescence in OA.\nMaterials and methods: We intersected osteoarthritis dataset GSE82107 from GEO database and senescence dataset from CellAge database of human senescence-associated genes based on genetic manipulations experiments plus gene expression profilin, and screened out 4 overlapping genes. The hub genes were verified in vitro and in human OA cartilage tissues by qRT-PCR. We further confirmed the function of mitogen-activated protein kinase 12 (MAPK12) and Fos proto-oncogene (FOS) in OA in vitro and in vivo by qRT-PCR, western blotting, Edu staining, immunofluorescence, SA-β-gal staining, HE, IHC, von frey test, and hot plate.\nResults: 1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated. The expression of MAPK12 was obviously downregulated, whereas the expression profiles of FOS, CYR61 and TNFSF15 were remarkedly upregulated in H2O2- or IL-1β-stimulated C28/I2 cells, human OA cartilage tissues, and knee cartilage of aging mice. Furthermore, both MAPK12 over-expression and FOS knock-down can promote cell proliferation and cartilage anabolism, inhibit cell senescence and cartilage catabolism, relieve joint pain in H2O2- or IL-1β-stimulated C28/I2 cells and mouse primary chondrocytes, destabilization of the medial meniscus (DMM) mice.\nConclusion: This study explored that MAPK12 and FOS are involved in the occurrence and development of OA through modulating chondrocyte senescence. They might be biomarkers of OA chondrocyte senescence, and provides some evidence as subsequent possible therapeutic targets for OA.\nThe translational potential of this article: The translation potential of this article is that we revealed MAPK12 and FOS can effectively alleviate OA by regulating chondrocyte senescence, and thus provided potential therapeutic targets for prevention or treatment of OA in the future.", "claims": [{"id": "claim-method", "statement": "The GSE82107 dataset was analysed using “R\" to filter out genes satisfying |log2(FC)|>1.5 & p < 0.05, then volcano and heat maps were constructed. Our analyses were performed in the R statistical (4.0.2). Data were statistically analyzed using GraphPad Prism 9.0 software and presented as mean ± SD. An unpaired t-test was applied while comparing two groups with one variance. Multiple comparisons were carried out using one-way ANOVA test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39007035", "locator": "sections[4] \"Identification of DEGs, GO and KEGG pathway analysis\" paragraph 2", "quote": "The GSE82107 dataset was analysed using “R\" to filter out genes satisfying |log2(FC)|>1.5 & p < 0.05, then volcano and heat maps were constructed."}, {"asset": "source:pmid:39007035", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "Our analyses were performed in the R statistical (4.0.2)."}, {"asset": "source:pmid:39007035", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "Data were statistically analyzed using GraphPad Prism 9.0 software and presented as mean ± SD."}, {"asset": "source:pmid:39007035", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "An unpaired t-test was applied while comparing two groups with one variance."}, {"asset": "source:pmid:39007035", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "Multiple comparisons were carried out using one-way ANOVA test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We searched the GEO database for “Osteoarthritis and Human” and obtained the GSE82107 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE82107) [15], which consisted of 7 normal samples and 10 OA samples, and divided them into control and OA groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39007035", "locator": "sections[3] \"OA microarray data\" paragraph 2", "quote": "We searched the GEO database for “Osteoarthritis and Human” and obtained the GSE82107 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE82107) [15], which consisted of 7 normal samples and 10 OA samples, and divided them into control and OA groups."}], "state": "complete"}, {"id": "claim-target-result", "statement": "1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39007035", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated.", "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:39007035"], "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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Results: 1458"], "order_basis": "paper_text_order:870", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["hermore, both MAPK12 over-expression and FOS knock-down can promote cell proliferation and cartilage", "joint of mice. MAPK12 over-expressing or FOS knock-down adenovirus was administered 10 μl by intra-a"], "order_basis": "paper_text_order:1545", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["r Chuanju Liu from New York university) were cultured in Dulbecco's modified Eagle medium (DMEM) cont", "age into collagenase II, digested cells were cultured in F12/DMEM containing 10 % fetal bovine serum"], "order_basis": "paper_text_order:2503", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The GSE82107 dataset was analysed using “R\" to filter out genes satisfying |log2(FC)|>1.5 & p < 0.05, then volcano and heat maps were constructed. 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