Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (3): 10-17.doi: 10.6040/j.issn.1671-7554.0.2020.1075

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Bioinformatic analysis of genes and molecular pathways associated with osteoarthritis synovitis

HUA Fang1,2, ZHANG Weiwei1,2, LYU Bo1,2, XIN Wei1,2   

  1. 1. Department of Clinical Laboratory;
    2. Department of Central Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China
  • Published:2021-04-06

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Abstract: Objective To identify the differentially expressed genes(DEGs)associated with the progression of osteoarthritis synovitis by bioinformatic analysis. Methods The gene expression profiles of GSE55457, GSE55235 and GSE12021 were downloaded from the Gene Expression Omnibus(GEO)to screen related genes in the pathogenesis of osteoarthritis. After the DEGs were identified, heatmaps were drawn, and functional enrichment of GO and KEGG was analyzed. The protein-protein interaction network(PPI)was constructed with STRING and Cytoscape, top module was screened with MCODE plug-in unit, and hub genes were screened with cytoHubba plug-in unit. Results There were 72 upregulated genes and 151 downregulated genes in the GSE55457, GSE55235 and GSE12021 gene expression profiles. GO analysis showed DEGs were involved in leukocyte migration, response to glucocorticoid, glycosaminoglycan binding, endoplasmic reticulum lumen, and nuclear outer membrane. KEGG analysis revealed DEGs were involved in MAPK signaling pathway, osteoclast differentiation and TNF signaling pathway. The cytoHubba screened out 10 key genes, including IL6, TLR7, SELE, VEGFA, LDLR, JUN, MYC, CD44, SNAI1 and hnRNA1. Conclusion Bioinformatic analysis can help to discover the molecular mechanism and key genes of synovitis in patients with osteoarthritis.

Key words: Osteoarthritis, Bioinformatics, Differentially expressed genes

CLC Number: 

  • R684.3
[1] Dillon CF, Rasch EK, Gu Q, et al. Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991-94 [J]. J Rheumatol, 2006, 33(11): 2271-2279.
[2] 窦晓丽, 段晓琴, 夏玲, 等. 骨关节炎: 关节软骨退变的相关研究与进展[J]. 中国组织工程研究与临床康复, 2011, 15(20): 3763-3766. DOU Xiaoli, DUAN Xiaoqin, XIA Ling, et al. Osteoarthritis: Study and progress in articular cartilage degeneration [J]. Journal of Clinical Rehabilitative Tissue Engineering Research, 2011, 15(20): 3763-3766.
[3] Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis [J]. Nat Rev Rheumatol, 2016, 12(7): 412-420.
[4] Cascone P, Vetrano S, Nicolai G, et al. Temporomandibular joint biomechanical restrictions: the fluid and synovial membrane [J]. J Craniofacial Surg,1999, 10(4): 301-307.
[5] Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis [J]. Bone, 2012, 51(2): 249-257.
[6] Bondeson J, Blom AB, Wainwright S, et al. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis [J]. Arthritis Rheum, 2010, 62(3): 647-657.
[7] Ayral X, Pickering EH, Woodworth TG, et al. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis-results of a 1 year longitudinal arthroscopic study in 422 patients [J]. Osteoarthritis and Cartilage, 2005, 13(5): 361-367.
[8] Geyer M, Schönfeld C. Novel insights into the pathogenesis of osteoarthritis [J]. Curr Rheumatol Rev, 2018, 14(2): 98-107.
[9] 魏庆娟, 闫永楠, 孔波, 等. 微阵列技术的应用及发展趋势[J]. 东北电力大学学报, 2008, 28(6): 17-21. WEI Qingjuan, YAN Yongnan, KONG Bo, et al. Application and development trend of micro-array technology [J]. Journal of Northeast Electric Power University, 2008, 28(6): 17-21.
[10] Li L, Lei Q, Zhang S, et al. Screening and identification of key biomarkers in hepatocellular carcinoma: Evidence from bioinformatic analysis [J]. Oncol Rep, 2017, 38(5): 2607-2618.
[11] Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets: update [J]. Nucleic Acids Res, 2013, 41(database issue): D991-D995. doi: 10.1093/nar/gks1193.
[12] Li WC, Bai DL, Xu Y, et al. Identification of differentially expressed genes in synovial tissue of rheumatoid arthritis and osteoarthritis in patients [J]. J Cell Biochem, 2019, 120(3): 4533-4544.
[13] Ashburner M, Ball CA, Blake JA, et al. Gene Ontology: tool for the unification of biology. The Gene Ontology Consortium [J]. Nat Genet, 2000, 25(1): 25-29.
[14] 李向真, 刘子朋, 李娟, 等. KEGG数据库的进展及其在生物信息学中的应用[J]. 药物生物技术, 2012, 19(6): 535-539. LI Xiangzhen, LIU Zipeng, LI Juan, et al. Recent progress and application of KEGG database in the research of bioinformatics [J]. Chinese Journal of Pharmaceutical Biotechnology, 2012, 19(6): 535-539.
[15] Woetzel D, Huber R, Kupfer P, et al. Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation [J]. Arthritis Res Ther, 2014, 16(2): R84.
[16] Huber R, Hummert C, Gausmann U, et al. Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane [J]. Arthritis Res Ther, 2008, 10(4): R98.
[17] McQuitty, Louis L. Similarity analysis by reciprocal pairs for discrete and continuous data [J]. Educational and Psychological Measurement, 1966, 26(4): 825-831.
[18] Martel-Pelletier J, Wildi LM, Pelletier JP. Future therapeutics for osteoarthritis [J]. Bone, 2012, 51(2): 297-311.
[19] Wadi L, Meyer M, Weiser J, et al. Impact of outdated gene annotations on pathway enrichment analysis [J]. Nat Methods, 2016, 13(9): 705-706.
[20] 范素芳, 王文雅, 张柳. 丝裂原活化蛋白激酶信号通路对骨关节炎软骨的作用[J]. 中国组织工程研究, 2012, 16(37): 7015-7019. FAN Sufang, WANG Wenya, ZHANG Liu.Effect of mitogen-activated protein kinases signaling pathway on osteoarthritis cartilage [J]. Chinese Journal of Tissue Engineering Research, 2012, 16(37): 7015-7019.
[21] Morita Y, Ito H, Ishikawa M, et al. Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model [J]. J Orthop Res, 2018, 36(7): 1959-1968.
[22] Lin C, Shao Y, Zeng C, et al. Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis [J]. Journal of Cellular Physiology, 2018, 233(8): 6135-6147.
[23] Lepetsos P, Papavassiliou KA, Papavassiliou AG. Redox and NF-κB signaling in osteoarthritis [J]. Free Radic Biol Med, 2019, 132: 90-100. doi: 10.1016/j.freeradbiomed.
[24] 王景红, 夏坤, 张志千, 等. 骨关节炎相关细胞因子及生物标志物的研究进展[J]. 中国实验方剂学杂志, 2015, 21(10): 225-230. WANG Jinghong, XIA Kun, ZHANG Zhiqian, et al. Research progress of osteoarthritis-related cytokines and biomarkers [J]. China Journal of Experimental Traditional Medical Formulae, 2015, 21(10): 225-230.
[25] Livshits G, Zhai G, Hart DJ, et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford Study [J]. Arthritis Rheum, 2009, 60(7): 2037-2045.
[26] 罗玉明, 郑维篷, 魏合伟. 骨关节炎与细胞因子TNF-α、IL-6关系的研究进展[J]. 现代诊断与治疗, 2013, 24(2): 326-327. LUO Yuming, ZHENG Weipeng, WEI Hewei. Research progress on the relationship of osteoarthritis with TNF-α, IL-6 [J]. Modern Diagnosis and Treatment, 2013, 24(2): 326-327.
[27] Guan M, Zhu Y, Liao B, et al. Low-intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis [J]. FEBS Open Bio, 2020, 10(3): 434-443.
[28] 王宁, 龙迪, 孟晓娜. IL-1β对小鼠软骨细胞中 c-myc 蛋白表达的影响[J]. 中华临床医师杂志(电子版), 2013, 24: 11486-11490. doi: 10.3877/cma.j.issn.1674-0785.2013.24.093. WANG Ning, LONG Di, MENG Xiaona. Effects of IL-1β on protein expression of c-myc in chondrocytes of mouse[J].Chinese Journal of Clinicians(Electronic Edition), 2013, 24: 11486-11490. doi: 10.3877/cma.j.issn.1674-0785.2013.24.093.
[29] Salter DM, Godolphin JL, Gourlay MS, et al. Analysis of human articular chondrocyte CD44 isoform expression and function in health and disease [J]. J pathol, 1996, 179(4): 396-402.
[30] Loeser RF, Chubinskaya S, Pacione C, et al. Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor 1 and osteogenic protein 1 in adult human articular chondrocytes[J]. Arthritis Rheum, 2005, 52(12): 3910-3917.
[31] Johnson GL, Nakamura K. The c-Jun kinase/stress-activated pathway: regulation, function and role in human disease [J]. Biochim Biophys Acta, 2007, 1773(8): 1341-1348.
[32] Loeser RF, Erickson EA, Long DL. Mitogen-activated protein kinases as therapeutic targets in osteoarthritis [J]. Curr Opin Rheumatol, 2008, 20(5): 581-586.
[33] Lee JY, Kang MJ, Choi JY, et al. Apolipoprotein B binds to enolase-1 and aggravates inflammation in rheumatoid arthritis [J]. Ann Rheum Dis, 2018, 77(10): 1480-1489.
[34] Chamberlain ND, Kim SJ, Vila OM, et al. Ligation of TLR7 by rheumatoid arthritis synovial fluid single strand RNA induces transcription of TNFα in monocytes [J]. Ann Rheum Dis, 2013, 72(3): 418-426.
[35] Hoshikawa N, Sakai A, Takai S, et al. Targeting extracellular miR-21-TLR7 signaling provides long-lasting analgesia in osteoarthritis [J]. Mol Ther Nucleic Acids, 2020, 19: 199-207. doi: 10.1016/j.omtn.2019.11.011.
[36] Wang H, Xu Y, Jin M, et al. SELE downregulation suppresses mast cell accumulation to protect against inflammatory response in chronic idiopathic urticaria [J]. Int Arch Allergy Immunol, 2021, 182(2): 83-93.
[37] Sun JX, Chang TF, Li MH, et al. SNAI1, an endothelial-mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization [J]. Angiogenesis, 2018, 21(3): 635-652.
[38] Roy R, Huang Y, Seckl MJ, et al. Emerging roles of hnRNA1 in modulating malignant transformation [J]. Wiley Interdiscip Rev RNA, 2017, 8(6): 10.
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