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人小关节组织的 Ingenuity 通路分析:对小关节骨关节炎的见解

Ingenuity pathway analysis of human facet joint tissues: Insight into facet joint osteoarthritis.

作者信息

Chen Chu, Cui Shengyu, Li Weidong, Jin Huricha, Fan Jianbo, Sun Yuyu, Cui Zhiming

机构信息

Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

出版信息

Exp Ther Med. 2020 Apr;19(4):2997-3008. doi: 10.3892/etm.2020.8555. Epub 2020 Feb 26.

Abstract

Facet joint osteoarthritis (FJOA) is a common degenerative joint disorder with high prevalence in the elderly. FJOA causes lower back pain and lower extremity pain, and thus severely impacts the quality of life of affected patients. Emerging studies have focused on the histomorphological and histomorphometric changes in FJOA. However, the dynamic genetic changes in FJOA have remained to be clearly determined. In the present study, previously obtained RNA deep sequencing data were subjected to an ingenuity pathway analysis (IPA) and canonical signaling pathways of differentially expressed genes (DEGs) in FJOA were studied. The top 25 enriched canonical signaling pathways were identified and canonical signaling pathways with high absolute values of z-scores, specifically leukocyte extravasation signaling, Tec kinase signaling and osteoarthritis pathway, were investigated in detail. DEGs were further categorized by disease, biological function and toxicity (tox) function. The genetic networks between DEGs as well as hub genes in these functional networks were also investigated. It was demonstrated that C-X-C motif chemokine ligand 8, elastase, neutrophil expressed, growth factor independent 1 transcriptional repressor, Spi-1 proto-oncogene, CCAAT enhancer binding protein epsilon, GATA binding protein 1, TAL bHLH transcription factor 1, erythroid differentiation factor, minichromosome maintenance complex component 4, BTG anti-proliferation factor 2, BRCA1 DNA repair-associated, cyclin D1, chromatin assembly factor 1 subunit A, triggering receptor expressed on myeloid cells 1 and tumor protein p63 were hub genes in the top 5 IPA networks (with a score >30). The present study provides insight into the pathological processes of FJOA from a genetic perspective and may thus benefit the clinical treatment of FJOA.

摘要

小关节骨关节炎(FJOA)是一种常见的退行性关节疾病,在老年人中患病率很高。FJOA会导致下背部疼痛和下肢疼痛,从而严重影响受影响患者的生活质量。新兴研究聚焦于FJOA的组织形态学和组织形态计量学变化。然而,FJOA的动态基因变化仍有待明确确定。在本研究中,对先前获得的RNA深度测序数据进行了 Ingenuity 通路分析(IPA),并研究了FJOA中差异表达基因(DEG)的典型信号通路。确定了前25个富集的典型信号通路,并详细研究了z评分绝对值较高的典型信号通路,特别是白细胞外渗信号通路、Tec激酶信号通路和骨关节炎通路。DEG还按疾病、生物学功能和毒性(tox)功能进行了分类。还研究了DEG之间的基因网络以及这些功能网络中的枢纽基因。结果表明,C-X-C基序趋化因子配体8、中性粒细胞表达的弹性蛋白酶、生长因子独立1转录抑制因子、Spi-1原癌基因、CCAAT增强子结合蛋白ε、GATA结合蛋白1、TAL bHLH转录因子1、红细胞分化因子、微小染色体维持复合体成分4、BTG抗增殖因子2、BRCA1 DNA修复相关蛋白、细胞周期蛋白D1、染色质组装因子1亚基A、髓样细胞表达的触发受体1和肿瘤蛋白p63是前5个IPA网络(得分>30)中的枢纽基因。本研究从基因角度深入了解了FJOA的病理过程,因此可能有益于FJOA的临床治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b44/7086291/7cb5433a7f7f/etm-19-04-2997-g00.jpg

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