The role of interleukin 11 in bone resorption by rheumatoid synovial cells

白细胞介素11在类风湿滑膜细胞骨吸收中的作用

• 批准号: 11670444
• 负责人: SUGIYAMA Eiji
• 金额: $ 2.24万
• 依托单位: Toyama Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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/grant/KAKENHI-PROJECT-11670444/
• 关键词: Rheumatoid arthritis; Osteoclast; Interleukin-11; Synovial T cells; Synovial cells; 慢性関節リウマチ; 滑膜細胞; IL-11; 破骨細胞; Tリンパ球; 破骨細胞分化誘導因子; ODF; OCIF

Inflammatory bone resorption is an important factor for joint destruction of rheumatoid arthritis (RA). Since osteoclasts play important roles in the bone resorption, we examined about the mechanism of osteoclastogenesis in rheumatoid synovium. We first examined the effect of interleukin-ll on the expression of receptor activator of NF-_κB ligand (RANKL), which is a critical protein for osteoclastogenesis, in rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts expressed small amounts of RANKL mRNA, as assessed by RT-PCR analysis. IL-11 enhanced the RANKL expression at a concentration of 10 ng/ml. In contrast, IL-11 did not affect the production of osteoprotegerin (OPG), a decoy receptor for RANK. These results suggested that IL-11 might be involved in osteoclastogenesis in rheumatoid synovium via enhanced expression of RANKL in rheumatoid synovial cells. We next examined the effect of synovial T cells on osteoclastogenesis in rheumatoid synovium because synovial T cells are known to strongly express RANKL protein. We found that the co-culture of synovial macrophages and synovial T cells resulted in the generation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated giant cells (TRAP-MGCs), and that RANKL-mediated signaling may be partially involved in the generation of TRAP-MGCs. Although the generated TRAP-MGCs could not resorb a dentine, it is likely that these cells have the ability to differentiate to osteoclast. These findings provide new insights in the osteoclastogenesis in rheumatoid synovium.

炎性骨吸收是类风湿关节炎（RA）关节破坏的重要因素。由于破骨细胞在骨吸收过程中起重要作用，我们探讨了类风湿关节炎滑膜中破骨细胞的发生机制。我们首先检测了白细胞介素-II对类风湿性滑膜成纤维细胞中NF-κB配体受体激活因子（RANKL）表达的影响，RANKL是破骨细胞生成的关键蛋白。通过RT-PCR分析评估，风湿性关节炎滑膜成纤维细胞表达少量RANKL mRNA。IL-11在10 ng/ml浓度下增强RANKL表达。相反，IL-11不影响骨保护素（OPG）的产生，OPG是RANK的诱饵受体。这些结果表明，IL-11可能通过增强类风湿滑膜细胞中RANKL的表达而参与类风湿滑膜中破骨细胞的生成。我们接下来检查了滑膜T细胞对类风湿性滑膜中破骨细胞生成的影响，因为已知滑膜T细胞强烈表达RANKL蛋白。我们发现，滑膜巨噬细胞和滑膜T细胞的共培养导致抗酒石酸酸性磷酸酶（TRAP）阳性多核巨细胞（TRAP-MGCs）的产生，RANKL介导的信号可能部分参与TRAP-MGCs的产生。虽然产生的TRAP-MGCs不能再吸收牙本质，但这些细胞可能具有分化为破骨细胞的能力。这些发现为类风湿性关节炎滑膜中破骨细胞的发生提供了新的认识。

项目成果

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Araya J、Maruyama M、Sassa K、Fujita T、Hayashi R、Matsui S、Kashii T、Yamashita N、Sugiyama E、Kobayashi M：“电离辐射增强人肺上皮细胞中基质金属蛋白酶 2 的产生”Am J 生理学肺细胞

Sugiyama E, Ikemoto M, Taki H, Maruyama M, Yamashita N, Kobayashi M: "Mizoribine, an inhibitor of inosine monophosphate dehydrogenase, inhibits interleukin-6 production by freshly prepared rheumatoid synovial cells"Mod Rheumatol. 11. 28-33 (2001)

Sugiyama E、Ikemoto M、Taki H、Maruyama M、Yamashita N、Kobayashi M：“Mizoribine 是一种肌苷单磷酸脱氢酶抑制剂，可抑制新鲜制备的类风湿滑膜细胞产生白细胞介素 6”Mod Rheumatol。

Taki H., Sugiyama E., Kuroda A., Mino T., Kobayashi M.: "Interleukin-4 inhibits interlettkin-11 production by rheumatoid synovial cells"Rheumatology (former British J Rheumatol). 39. 728-731 (2000)

Taki H.、Sugiyama E.、Kuroda A.、Mino T.、Kobayashi M.：“Interleukin-4 抑制类风湿滑膜细胞产生 interlettkin-11”Rheumatology（前英国 J Rheumatol）。

Matsui S, Yamashita N, Mino T, Taki H, Sugiyama E, Hayashi R, Maruyama M, Kobayashi M: "Role of the endogenous prostaglandin E2 in human lung fibroblast interleukin-11 production"Respi Med. 93. 637-642 (1999)

Matsui S、Yamashita N、Mino T、Taki H、Sugiyama E、Hayashi R、Maruyama M、Kobayashi M：“内源性前列腺素 E2 在人肺成纤维细胞白细胞介素 11 产生中的作用”Respi Med。

Taki H., Sakai T., Sugiyama E., Mino T., Kuroda A., Taki K., Hamazaki T., Koizumi H., Kobayashi M: "Monokine stimulation of interleukin-11 production by human vascular smooth muscle cells in vitro"Atherosclerosis. 144. 375-380 (1999)

Taki H.、Sakai T.、Sugiyama E.、Mino T.、Kuroda A.、Taki K.、Hamazaki T.、Koizumi H.、Kobayashi M：“单核因子刺激人血管平滑肌细胞产生白细胞介素 11