{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:42:04Z","timestamp":1765953724196,"version":"3.48.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Knee osteoarthritis (KOA) is a prevalent chronic degenerative joint disease that causes chronic pain and mobility restrictions in the elderly, significantly impacting quality of life. Current treatments focus on symptom relief, lacking effective interventions targeting the underlying mechanisms. Understanding KOA\u2019s molecular mechanisms and identifying key pathogenic genes are essential for developing targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gene expression data from KOA patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to reveal the associated biological processes and signaling pathways. Protein-protein interaction (PPI) network analysis and Gene Ontology-based semantic similarity calculations were used to identify hub genes. Gene Set Variation Analysis (GSVA) assessed enrichment in KOA-related pathways. Immune infiltration analysis (CIBERSORT) assessed the immune cell distribution in KOA tissues. Finally, hub gene expression changes were validated using the IL-1\u03b2-treated CHON-001 cell model and real-time quantitative PCR (RT-qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 3,290 upregulated and 2,536 downregulated DEGs were identified. GO and KEGG enrichment analyses revealed these genes were primarily involved in extracellular matrix remodeling, transmembrane transport, and inflammation-related pathways. Key hub genes, including HSPA5, FOXO1, and YWHAE, were identified. GSVA showed that these genes were significantly enriched in multiple KOA-associated signaling pathways. Immune infiltration analysis revealed significant differences in the levels of six immune cell types in KOA tissues, which were associated with the hub genes expression. In CHON-001 cell, the expression levels of GRB2, IKBKG, and HSPA12A were upregulated, whereas YWHAE, HSPB1, and DCAF8 were downregulated, consistent with the tissue samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified key pathogenic genes and their regulatory pathways in KOA, highlighting their potential role in disease progression via inflammation and immune modulation. These findings provide insights for developing targeted therapeutic strategies for KOA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2025.1671693","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:37:17Z","timestamp":1765953437000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and functional analysis of hub genes in knee osteoarthritis via bioinformatics and experimental validation"],"prefix":"10.3389","volume":"5","author":[{"given":"Shanyong","family":"Jiang","sequence":"first","affiliation":[]},{"given":"Jingjing","family":"Cao","sequence":"additional","affiliation":[]},{"given":"Jianshu","family":"Lu","sequence":"additional","affiliation":[]},{"given":"Jianxiao","family":"Liang","sequence":"additional","affiliation":[]},{"given":"Lianxin","family":"Li","sequence":"additional","affiliation":[]},{"given":"Yanqiang","family":"Song","sequence":"additional","affiliation":[]},{"given":"Jincheng","family":"Gao","sequence":"additional","affiliation":[]},{"given":"Baoen","family":"Jiang","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.mcna.2019.10.007","article-title":"Osteoarthritis: pathology, diagnosis, and treatment options","volume":"104","author":"Abramoff","year":"2020","journal-title":"Med. Clin. North Am."},{"key":"B2","first-page":"223","volume-title":"Macrophage Inflammatory Protein-1 Alpha (MIP-1 alpha)\/CCL3: As a Biomarker","author":"Bhavsar","year":"2015"},{"key":"B3","doi-asserted-by":"publisher","first-page":"82S","DOI":"10.1177\/1947603520942941","article-title":"Synovial fluid biomarkers in knee osteoarthritis: a systematic review and quantitative evaluation using BIPEDs criteria","volume":"13","author":"Boffa","year":"2021","journal-title":"Cartilage"},{"key":"B4","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1177\/0269215517691084","article-title":"The Ottawa panel clinical practice guidelines for the management of knee osteoarthritis. Part two: strengthening exercise programs","volume":"31","author":"Brosseau","year":"2017","journal-title":"Clin. Rehabil."},{"key":"B5","first-page":"169","article-title":"Synovial inflammation in patients with different stages of knee osteoarthritis","volume":"56","author":"Ene","year":"2015","journal-title":"Rom. J. Morphol. Embryol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"6405","DOI":"10.3390\/ijms24076405","article-title":"Knee osteoarthritis: epidemiology, pathogenesis, and mesenchymal stem cells: what else is new? An update","volume":"24","author":"Giorgino","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B7","first-page":"1308","article-title":"Research progress of the regulation mechanism of inflammatory factors and signaling pathways in osteoarthritis of the knee","author":"He","year":"2019","journal-title":"Chin. J. Clin. Pharmacology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1136\/annrheumdis-2020-218089","article-title":"Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis","volume":"80","author":"Hu","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s13018-024-04660-9","article-title":"Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis","volume":"19","author":"Huang","year":"2024","journal-title":"J. Orthop. Surg. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"127","DOI":"10.12809\/hkmj187600","article-title":"Non-surgical treatment of knee osteoarthritis","volume":"25","author":"Kan","year":"2019","journal-title":"Hong Kong Med. J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3389\/fmed.2020.00304","article-title":"The prevalence of symptomatic knee osteoarthritis in relation to age, sex, area, region, and body mass index in China: a systematic review and meta-analysis","volume":"7","author":"Li","year":"2020","journal-title":"Front. Med. (Lausanne)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.molimm.2023.05.001","article-title":"HSPA5, as a ferroptosis regulator, may serve as a potential therapeutic for head and neck squamous cell carcinoma","volume":"158","author":"Li","year":"2023","journal-title":"Mol. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41419-023-05972-0","article-title":"HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-\u03baB signaling pathway in breast cancer","volume":"14","author":"Liang","year":"2023","journal-title":"Cell Death Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1177\/03635465221073991","article-title":"Exosomes derived from human urine-derived stem cells overexpressing miR-140-5p alleviate knee osteoarthritis through downregulation of VEGFA in a rat model","volume":"50","author":"Liu","year":"2022","journal-title":"Am. J. Sports Med."},{"key":"B15","first-page":"1006","article-title":"Progress of pathogenesis and treatment progress of osteoarthritis","author":"Luo","year":"2024","journal-title":"Shaanxi Med. Journal"},{"key":"B16","doi-asserted-by":"publisher","first-page":"5027","DOI":"10.3390\/jcm10215027","article-title":"Synovial fluid cytokines, chemokines and MMP levels in osteoarthritis patients with knee pain display a profile similar to many rheumatoid arthritis patients","volume":"10","author":"Meehan","year":"2021","journal-title":"J. Clin. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"555","DOI":"10.13703\/j.0255-2930.20230901-k0001","article-title":"Mechanism of acupotomy on chondrocyte ferroptosis in rabbits with knee osteoarthritis based on HSPA5\/GPX4 signaling pathway","volume":"44","author":"Meng","year":"2024","journal-title":"Zhongguo Zhen Jiu"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1249\/MSS.0000000000000293","article-title":"Knee joint loading in knee osteoarthritis: influence of abdominal and thigh fat","volume":"46","author":"Messier","year":"2014","journal-title":"Med. Sci. Sports Exerc"},{"key":"B19","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3390\/life13020342","article-title":"Soluble and EV-Associated diagnostic and prognostic biomarkers in knee Osteoarthritis pathology and detection","volume":"13","author":"Moravek","year":"2023","journal-title":"Life"},{"key":"B20","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1007\/s00167-014-3360-3","article-title":"Correlation between varus knee malalignment and patellofemoral osteoarthritis","volume":"24","author":"Otsuki","year":"2016","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e2101661","DOI":"10.1002\/adhm.202101661","article-title":"Long-term recruitment of endogenous M2 macrophages by platelet lysate-rich plasma macroporous Hydrogel scaffold for articular cartilage defect repair","volume":"11","author":"Pan","year":"2022","journal-title":"Adv. Healthc. Mater"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1007\/s00005-011-0115-4","article-title":"CXCL8 and CCL5 expression in synovial fluid and blood serum in patients with osteoarthritis of the knee","volume-title":"Archivum immunologiae et therapiae experimentalis -English edition-","author":"Pierzchala","year":"2011"},{"key":"B23","doi-asserted-by":"publisher","first-page":"287","DOI":"10.2174\/1573397118666220928141624","article-title":"Mesenchymal cells are a promising -But still Unsatisfying- Anti- inflammatory therapeutic strategy for osteoarthritis: a narrative review","volume":"19","author":"Rosini","year":"2023","journal-title":"Curr. Rheumatol. Rev."},{"key":"B24","first-page":"1291","article-title":"The subspecialty group of osteoarthritis CAO","volume":"41","author":"Surgeons","year":"2021"},{"key":"B25","doi-asserted-by":"publisher","first-page":"207","DOI":"10.2519\/jospt.2022.10490","article-title":"Similar effects of exercise therapy, nonsteroidal anti-inflammatory drugs, and opioids for knee osteoarthritis pain: a systematic review with network meta-analysis","volume":"52","author":"Thorlund","year":"2022","journal-title":"J. Orthop. Sports Phys. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1177\/1941738119887183","article-title":"The role of resistance training dosing on pain and physical function in individuals with knee osteoarthritis: a systematic review","volume":"12","author":"Turner","year":"2020","journal-title":"Sports Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1557S","DOI":"10.1177\/1947603520958149","article-title":"Clusterin is associated with systemic and synovial inflammation in knee osteoarthritis","volume":"13","author":"Ungsudechachai","year":"2021","journal-title":"CARTILAGE"},{"key":"B28","doi-asserted-by":"publisher","first-page":"111496","DOI":"10.1016\/j.intimp.2024.111496","article-title":"Single-cell RNA sequencing reveals the impact of mechanical loading on knee tibial cartilage in osteoarthritis","volume":"128","author":"Wang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s13287-024-03870-6","article-title":"Human adipose and synovial-derived MSCs synergistically attenuate osteoarthritis by promoting chondrocyte autophagy through FoxO1 signaling","volume":"15","author":"Wu","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1186\/s13018-023-04375-3","article-title":"Cross-cultural adaptation and validation for central sensitization inventory: based on Chinese patients undergoing total knee arthroplasty for knee osteoarthritis","volume":"18","author":"Xu","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0284274","DOI":"10.1371\/journal.pone.0284274","article-title":"Comparative analysis of gene ontology-based semantic similarity measurements for the application of identifying essential proteins","volume":"18","author":"Xue","year":"2023","journal-title":"PLoS One"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.2147\/DDDT.S211051","article-title":"Downregulation of microRNA-23b-3p alleviates IL-1beta-induced injury in chondrogenic CHON-001 cells","volume":"13","author":"Yang","year":"","journal-title":"Drug Des. Devel Ther."},{"key":"B33","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41434-019-0068-5","article-title":"Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-\u03baB signaling pathway by regulating CCL4 in osteoarthritis","volume":"26","author":"Yang","year":"","journal-title":"Gene Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"118930","DOI":"10.1016\/j.jep.2024.118930","article-title":"Yiqi yangxue formula inhibits cartilage degeneration in knee osteoarthritis by regulating LncRNA-UFC1\/miR-34a\/MMP-13 axis","volume":"337","author":"Zhao","year":"2025","journal-title":"J. Ethnopharmacology"}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1671693\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:37:22Z","timestamp":1765953442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1671693\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":34,"alternative-id":["10.3389\/fbinf.2025.1671693"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2025.1671693","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"article-number":"1671693"}}