Analysis of pathological role of RA Nurse-like cells in Joint destruction of RA

RA Nurse样细胞在RA关节破坏中的病理作用分析

• 批准号: 11470309
• 负责人: OCHI Takahiro
• 金额: $ 10.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470309/
• 关键词: rheumatoid arthritis; Nurse-like cells; bone marrow; pseudoemperipolesis; elongation factor 1 alpha; osteoclast-like cell; bone and cartilage degradation; pseudoemperipolesis; 破骨細胞; MMP; カテプシン

We have established RA Nurse-Like Cell (RANC) characterized by pseudoemperipolesis from synovial tissues and bone marrow of patients with RA.RANC has various potential ; a nursing ability for lymphocytes from bone marrow and synovium of RA patients, production of hyaluronan etc, and was thought to play an pivotal role in pathomechanism of RA.In this study we investigated further effects of RANC in the pathogenesis of RA.1. We have cloned the novel gene specific for RANC ; NSR, #4-142. B lymphocyte cocultured with RANC is producing antibody, one of which is appeared to be anti elongation factor 1 alpha antibody.3. We have shown that mononuclear cells in RA synovial fluid could differentiate into osteoclast-like cell (OCL) which was positive for TRAP stain, have a ability of bone resorption and fulfils another osteoclastic characters. We have also established OCL from peripheral blood monocytes with support of RANC.4. In vivo analysis of RANC cocultured with mononuclear cells or B cells on articular cartilage showed severe degradation of cartilage but normal skin fibroblast caused almost no erosions.In conclusion, RANC may play an important role in both bone and cartilage destruction and contribute the pathomachanism of RA.

我们从RA患者的滑膜组织和骨髓中建立了以假胚泡形成为特征的RA护士样细胞（RANC），RANC具有多种潜能，如对RA患者骨髓和滑膜中淋巴细胞的护理能力、透明质酸的产生等，被认为在RA的发病机制中起着关键作用.我们已经克隆了RANC特异性的新基因; NSR，#4-142。与RANC共培养的B淋巴细胞正在产生抗体，其中一种似乎是抗延伸因子1 α抗体。3.我们发现RA滑液中的单个核细胞可分化为TRAP阳性的破骨细胞样细胞（OCL），具有骨吸收能力，并具有另一种骨细胞特性。我们还建立了OCL从外周血单核细胞的支持下，RANC。RANC与单核细胞或B细胞在关节软骨上共培养的体内分析显示，软骨严重降解，而正常皮肤成纤维细胞几乎没有引起侵蚀。结论：RANC可能在骨和软骨破坏中发挥重要作用，并参与RA的发病机制。

项目成果

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Shi K，Ochi T.：“类风湿性关节炎的足部畸形与疾病严重程度的相关性。”J Rheumatol。

Nishimoto N, Tomita T, Ochi T, et al.: "IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor"Int Immunol. 12. 187-193 (2000)

Nishimoto N、Tomita T、Ochi T 等人：“在可溶性 IL-6 受体存在的情况下，IL-6 会抑制类风湿性关节炎患者的成纤维细胞滑膜细胞的增殖”。

Hirohata S, Tomita T, Ochi T, et al.: "Suppressive influences of methotrexate on the generation of CD14(+) monocyte-lineage cells from bone marrow of patients with rheumatoid arthritis"Clin Immunol. 91. 84-89 (1999)

Hirohata S、Tomita T、Ochi T 等人：“甲氨蝶呤对类风湿性关节炎患者骨髓中 CD14(+) 单核细胞谱系细胞生成的抑制作用”Clin Immunol。

Iijima T, Tomita T, Ochi T, et al.: "Incidence of postpartum onset disease among patients with rheumatoid arthritis"J Rheumatol. 26. 755-756 (1999)

Iijima T、Tomita T、Ochi T 等人：“类风湿性关节炎患者产后发病率”J Rheumatol。

Tomita T,Ochi T.: "Transcription Factor Decoy for NFkB Inhibits Cytokine and Adhesion Molecule Expressions in Synovial Cells Derived from Rheumatoid Arthritis. "Rheumarology. 39(7). 749-57 (2000)

Tomita T，Ochi T.：“NFkB 转录因子诱饵抑制类风湿性关节炎滑膜细胞中的细胞因子和粘附分子表达。”风湿病学。