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骨关节炎和类风湿关节炎中关键分子及信号通路分析。

Analysis of critical molecules and signaling pathways in osteoarthritis and rheumatoid arthritis.

机构信息

Department of Orthopaedics, Fengxian Central Hospital, Shanghai 201400, P.R. China.

出版信息

Mol Med Rep. 2013 Feb;7(2):603-7. doi: 10.3892/mmr.2012.1224. Epub 2012 Dec 4.

DOI:10.3892/mmr.2012.1224
PMID:23232804
Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most prevalent forms of arthritis in the elderly. This study aimed to explore the molecular mechanisms of these diseases and identify underlying therapeutic targets. Using GSE1919 microarray data sets downloaded from the Gene Expression Omnibus database, we screened differentially expressed genes (DEGs) in OA and RA cells. The underlying molecular mechanisms of these crucial genes were investigated by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Small molecule expression and SNP analysis were also conducted by searching CMap and dbSNP databases. More than 320 genes changed in the arthritic cells and there were only 196 DEGs between OA and RA. OA and RA activated the classic mitogen-activated protein kinase signaling pathway, insulin signaling pathway, antigen processing and presentation and intestinal immune network for IgA production. Graft-versus-host disease and autoimmune thyroid disease-related pathways were also activated in OA and RA. Parthenolide and alsterpaullone may be treatments for OA and RA and insulin-like growth factor 1, collagen α2(I) chain and special AT-rich sequence-binding protein 2 may be critical SNP molecules in arthritis. Our findings shed new light on the common molecular mechanisms of OA and RA and may provide theoretical support for further clinical therapeutic studies.

摘要

骨关节炎(OA)和类风湿关节炎(RA)是老年人最常见的关节炎形式。本研究旨在探索这些疾病的分子机制,并确定潜在的治疗靶点。我们使用从基因表达综合数据库(GEO)下载的 GSE1919 微阵列数据集,筛选 OA 和 RA 细胞中的差异表达基因(DEG)。通过京都基因与基因组百科全书通路富集分析研究这些关键基因的潜在分子机制。还通过搜索 CMap 和 dbSNP 数据库进行小分子表达和 SNP 分析。在关节炎细胞中改变了超过 320 个基因,而 OA 和 RA 之间只有 196 个 DEG。OA 和 RA 激活了经典的丝裂原活化蛋白激酶信号通路、胰岛素信号通路、抗原加工和呈递以及 IgA 产生的肠道免疫网络。移植物抗宿主病和自身免疫性甲状腺疾病相关通路也在 OA 和 RA 中被激活。小白菊内酯和阿尔特普醇可能是 OA 和 RA 的治疗方法,胰岛素样生长因子 1、胶原 α2(I)链和特殊富含 AT 的序列结合蛋白 2 可能是关节炎的关键 SNP 分子。我们的发现为 OA 和 RA 的共同分子机制提供了新的见解,并可能为进一步的临床治疗研究提供理论支持。

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