A New Function of The Lubricin and It's Role in the Pathogenesis of Arthritis.

Lubricin的新功能及其在关节炎发病机制中的作用。

• 批准号: 17591585
• 负责人: YAMAMOTO Takuya
• 金额: $ 2.24万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591585/
• 关键词: Lubricin; Rheumatoid Arthritis; sMSF protein; Hyaluronic acid; 蛋白質; 免疫学

We previously found that the lubricin mRNA deleting the exon 6 (sMSF) is present in synovial fluids from rheumatoid arthritis (RA). To detect the sMSF protein, rabbit anti-human lubricin polyclonal antibody was produced immunizing the purified lubricin, and that reactivity with lubricin and sMSF recombinant protein were confirmed. In the detection of sMSF using that antibody and western blotting, a lot of the sMSF protein was present in synovial fluids from RA patients in comparison with that from OA patients.The presence of the complex of lubricin and hyaluronic acid (HA) has not been clarified in vivo. Therefore, we tried to examine that complex in synovial fluids from RA and OA patients. The molecular weight (M.W.) of lubricin was ranged from 300 kDa to 5,000 kDa in RA and OA synovial fluids in the fractionation using Sepharose-S 500. There was much of the lower M.W. lubricin in synovial fluids from RA patients than OA patients. To determine whether the high M.W. lubricin is the complex with HA, HA was trapped with HA binding protein (HABP) that is specifically bound to HA, and then, lubricin in the HABP binding proteins was detected using anti-lubricin antibody and western blotting. The results showed that lubricin in RA and OA synovial fluids was present in the complex with HA. In addition, we found that lubricin is bound to joint cartilage via HA.Recently, the high M.W. (3,000 kDa) or low M.W. (1,000 kDa) HA are available as a drug for treatment of arthritis. Thus, it is an interesting subject to know how these HA are contributed to the boundary lubrication by forming the complex with lubricin.

我们以前发现，润滑素mRNA删除外显子6（sMSF）是存在于滑液类风湿关节炎（RA）。为了检测sMSF蛋白，免疫纯化的润滑素制备兔抗人润滑素多克隆抗体，并证实其与润滑素和sMSF重组蛋白的反应性。在使用该抗体和蛋白质印迹法检测sMSF中，与OA患者相比，RA患者的滑液中存在大量sMSF蛋白，但体内润滑素和透明质酸（HA）复合物的存在尚未阐明。因此，我们试图检查RA和OA患者滑液中的复合物。分子量（M.W.）在使用Sepharose-S 500的分级分离中，RA和OA滑液中润滑素的范围为300 kDa至5，000 kDa。有很多低分子量的。RA患者滑液中的润滑素水平高于OA患者。为了确定高分子量物质是否存在。润滑素是与HA的复合物，HA被与HA特异性结合的HA结合蛋白（HABP）捕获，然后使用抗润滑素抗体和蛋白质印迹法检测HABP结合蛋白中的润滑素。结果表明，RA和OA滑液中的润滑素均存在于与HA的复合物中。此外，我们发现润滑素通过HA与关节软骨结合。最近，高分子量（3，000 kDa）或低分子量。（1，000 kDa）HA可用作治疗关节炎的药物。因此，了解这些HA是如何通过与润滑素形成复合物来促进边界润滑的是一个有趣的课题。

项目成果

The Z39Ig protein is a specific marker of synovial A cells in RA synovium

Z39Ig蛋白是RA滑膜中滑膜A细胞的特异性标志物

• 发表时间: 2006
• 期刊: Arthritis and Rheumatism 54・9
• 作者: Sakimura R;Tanaka K;Nakatani F;Matsunobu T;Li X;Hanada M;Okada T;Nakamura T;Iwamoto Y;Tanaka M
• 通讯作者: Tanaka M

In vitro in vivo efficacies of the recombinant immunotoxin against the folate receptor β on RA synovial cells

重组免疫毒素抗叶酸受体β对RA滑膜细胞的体外体内疗效

• 发表时间: 2006
• 期刊: Arthritis and Rheumatism 54・10
• 作者: Takahiro;USHIDA;et. al.;Nagai T
• 通讯作者: Nagai T

Expression of similar MSF variant in RA synovial fluids

RA滑液中类似MSF变体的表达

• 发表时间: 2006
• 期刊: Modern Rheumatology 16
• 作者: Tsuneyoshi Y;Yamamoto T;et al.
• 通讯作者: et al.