{"doi":"10.1016/j.joca.2025.08.013","title":"Cross-platform transcriptomic data integration identifies an overactive neuro-immune signature in human osteoarthritis synovium","abstract":"OBJECTIVE: Chronic synovitis is associated with osteoarthritis (OA) pain, but the molecular underpinnings remain unclear. Our objective was to characterize the transcriptional phenotype of OA synovium with a focus on signaling relevant to pain. DESIGN: Eight publicly-available microarray and RNA-sequencing GEO datasets from human non-OA and OA subjects underwent quality control and re-analysis for differentially-expressed genes (DEGs). Cross-platform statistical integration was performed via a weighted Z-test to combine detection power across datasets. Gene set enrichment, cell type enrichment, and regulon analyses were performed. Human single-cell RNA sequencing data was used to map gene expression to cell types. Ligand-receptor interactions were predicted via multi-omic data from human dorsal root ganglia (DRG). RESULTS: Following statistical integration of individual studies (N=153 total subjects, N=139 after quality control), gene set enrichment analysis identified 276 differentially-activated pathway terms in OA synovium, including strong enrichment for pathways related to innate and adaptive immunity (notably MHC Class II) and fibrotic remodeling-relevant extracellular matrix organization. VEGF signaling and angiogenesis-related terms were downregulated. Enriched pain and neuronal pathways primarily related to neuro-immune interactions, including neuroinflammation, and were associated with macrophages, B and T lymphocytes, and synovial fibroblasts. A gene regulatory network comprised of STAT1, FLI1, and VDR putatively governed the expression of 27 genes driving neuro-immune signaling. An unbiased synovium-DRG interactome predicted 76 potential interactions between synovial cells and DRG nociceptors, involving 68 neuronal receptors interacting with 32 ligands overexpressed in OA synovium. CONCLUSIONS: End-stage OA synovium is markedly enriched for neuroinflammatory and neuro-immune signaling, putatively governed by STAT1, FLI1, and VDR.","journal":"Osteoarthritis and Cartilage","year":2025,"id":518694,"datarank":0.35398400832621363,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.04206777707423818,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.04206777707423818,"corpus_percentile":50.05801810164771,"corpus_rank":6457,"citation_count":7,"citer_count":6,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6996,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":483825,"name":"Hannah Swahn","orcid":null,"position":1,"is_corresponding":false},{"id":226245,"name":"Dana E. Orange","orcid":"0000-0001-9859-7199","position":2,"is_corresponding":false},{"id":948431,"name":"Joseph B. Lesnak","orcid":"0000-0002-4098-9090","position":3,"is_corresponding":false},{"id":257966,"name":"Theodore J. Price","orcid":"0000-0002-6971-6221","position":4,"is_corresponding":false},{"id":353851,"name":"Anne‐Marie Malfait","orcid":"0000-0003-1428-0384","position":5,"is_corresponding":false},{"id":353852,"name":"Rachel E. Miller","orcid":"0000-0002-4486-5757","position":6,"is_corresponding":false},{"id":291598,"name":"Martin Lotz","orcid":"0000-0002-6299-8799","position":7,"is_corresponding":false},{"id":774769,"name":"Tristan Maerz","orcid":"0000-0002-4523-6012","position":8,"is_corresponding":false},{"id":1150883,"name":"Michael D. Newton","orcid":"0000-0003-1262-0613","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"40889615","pmcid":"PMC13112359","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":[]}