{"doi":"10.1101/2021.05.06.442993","title":"Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis","abstract":"Abstract Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the great majority of KOA seen clinically, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related KOA in murine model. Protein-level data together with transcriptomic profiling revealed inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of aged cartilage were unique from those in PTOA, with only 1% overlap between the two. At the nexus of aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as intrinsically linked to age-related KOA. This pathway was further validated by mass spectrometry. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a key driver of age-related KOA.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":224066,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9057,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":820069,"name":"Gabrielle Gilmer","orcid":"0000-0002-9039-4183","position":1,"is_corresponding":false},{"id":820070,"name":"Kai Wang","orcid":"0000-0001-8447-6177","position":2,"is_corresponding":false},{"id":629933,"name":"Sruthi Sivakumar","orcid":"0000-0003-0649-8551","position":3,"is_corresponding":false},{"id":467373,"name":"Christopher H. Evans","orcid":"0000-0001-5532-2347","position":4,"is_corresponding":false},{"id":825832,"name":"Yusuke Matsui","orcid":"0000-0003-3977-4313","position":5,"is_corresponding":false},{"id":435372,"name":"Fabrisia Ambrosio","orcid":"0000-0002-5497-5968","position":6,"is_corresponding":false},{"id":820068,"name":"Hirotaka Iijima","orcid":"0000-0001-5504-1502","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:14.760456Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}