Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis.
Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis.
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DOI：
10.3389/fimmu.2021.665442
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Zhao Y;Lv J;Zhang H;Xie J;Dai H;Zhang X
色素性绒毛结节性滑膜炎（PVNS）是一种罕见的滑膜组织良性增生的疾病，其特点是严重的关节破坏和手术切除后的高复发率。然而，对其发病机制的不了解限制了其有效治疗。本研究采用整合RNA测序（RNA-seq）和微阵列技术，分析了6例PVNS患者、11例骨关节炎（OA）患者、9例类风湿性关节炎（RA）患者（E-MTAB-6141）和3例健康受试者（GSE143514） PVNS转录组的基因表达谱。利用基因本体、基因串和细胞壁检测基因功能富集程度。采用流式细胞术或免疫组化检测细胞功能分子，鉴定细胞亚群和功能。分离CD14+细胞，诱导成破骨细胞，观察单核/巨噬细胞功能。PVNS最明显的局部表现是炎症，包括免疫细胞浸润和细胞因子分泌增加，以及肿瘤表型。高比例的炎症细胞，包括T细胞、自然杀伤细胞（NK）细胞、NKT细胞和B细胞从血液中被招募。PVNS滑膜中Th17和单核细胞，尤其是经典单核细胞而非非经典单核细胞增加。局部观察到破骨细胞生成和巨噬细胞活化明显增加。PVNS髓细胞中MMP9、SIGLEC 15、RANK的表达明显高于OA。与RA相比，破骨细胞分化和髓样细胞活化是PVNS特有的特征，而T细胞活化是PVNS和RA共有的。PVNS的转录表达特征表现为免疫应答、细胞迁移和破骨细胞发生增加。破骨细胞分化仅在PVNS中观察到，而在RA中没有观察到，而t细胞活化在炎症性关节炎中很常见。
Pigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy. In this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14+ cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function. The most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA. The transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.
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影响因子：
6.4
作者：
Lan, Yongsheng;Zhang, Yongyou;Wang, Jianghua;Lin, Chunhong;Ittmann, Michael M.;Wang, Fen
通讯作者：
Wang, Fen
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影响因子：
7.3
作者：
Mense SM;Barrows D;Hodakoski C;Steinbach N;Schoenfeld D;Su W;Hopkins BD;Su T;Fine B;Hibshoosh H;Parsons R
通讯作者：
Parsons R
影响因子：
3.8
作者：
Guo, QinWei;Shi, WeiLi;Hu, YueLin
通讯作者：
Hu, YueLin
影响因子：
3.2
作者：
Mulcahy, H;O'Rourke, KP;O'Gara, F
通讯作者：
O'Gara, F
影响因子：
82.9
作者：
Moore, RJ;Owens, DM;Balkwill, F
通讯作者：
Balkwill, F