Involvement of bone marrow interstitial fibroblastic cells which support the differentiation of CD(+) peripheral-blood monocytes into TRAP positive cells. In bone and cartilage destruction in rheumatoid arthritis.

骨髓间质成纤维细胞的参与支持 CD(+) 外周血单核细胞分化为 TRAP 阳性细胞。

• 批准号: 13470311
• 负责人: OCHI Takahiro
• 金额: $ 8.9万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470311/
• 关键词: rheumatoid arthritis; nurse cell; bone marrow; osteochondral destruction; TRAP-positive cell; 慢性関節リウマチ; 骨・軟骨破壊

We have shown the involvement of bone marrow lesion in joint destruction of the partents with rheumatoid arthritis. We found the process of the generation of these TRAP positive multinuclear cells in vitro. Which would be involved in pathogenesis of accelerated bone resorption in juxta-articular bone in RA patients. At first we found that marrow of RA patients have almost the same function with nurse cells which showed pseudoemperiporesis in mouse thymus. These marrow of RA patients have almost the same function with nurse cells which showed pseudoemperiporesis in mouse thymus. These cells. Nurse-like cells. From the synovial tissue and bone marrow of patients with RA support highly activated blood cells through pseudoemperiporesis. CD14(-)periphcral-blood monocytes from healthy individual are supported by co-cultured nurse-like cells from synovial tissues of patients with RA and activated and differentiated into TRAP positive mononuclear cells within 5 weeks of culture. These mononucl … More ear cells then fused and differentiated into multinucleared giant cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. These multinucleated giant cells have ability of forming pits on dentin slice which suggests the bone resorbing activity and express the vitronectin receptor. And carbonic anhydrase 11 by immunocytochemistry. These multinucleated giant cells have ability of forming pits on dentin slice which suggests the bone resorbing activity. These TRAP (+) mononuclear and multinucleated cells also expressed MMP-2 (gelatinase-A). MMP-9(gelatinase-B).MMP-12(macrophage metalloelastse) and MMP-14 (MT1-MMP) mPNA in RT-PCR and northern blot analysis. Immunocytochemistry for these MMPs showed that MMP-2 and MMP-9 and MMP-14 were produced by TRAP positive multinucleated cells. TRAP positive mononuclear cells also induced the release of S^<35> from relabeled cartilage discs. These results indicate that TRAP-positive mononuclear cells located in the synovium at the cartilage synovial interface produce MMP-2 and 9 and can play an important role in articular cartilage destruction. TRAP-positive multinucleated cells proliferated in the subchondral bone marrow space. Most of those are osteoclasts. Are closely associated to accelerated bone resorption in RA patients. Both TRAP-positive cells play main roles in joint destruction and supported by abundant fibroblast-like cells in the synovial tissues in joint and bone marrow space. On the other hand. The retardation of growth plate adjacent to affected joint in juvenile rheumatoid arthritis. We also showed that the growth plate was damaged in early stage of arthritis in collagen induced arthritic rats. The destruction of growth plate was not a sequence of the articular destruction but a event independent from articular synovitis in space and accompanied with the increased expression of MMP-3 and VGEF in hypertrohic cartilage cells. These findings also showed the bone marrow lesion involvement in growth plate destruction in arthritis. Less

我们已经证明骨髓病变参与了类风湿性关节炎患者的关节破坏。我们在体外发现了这些TRAP阳性多核细胞的产生过程。这可能参与了类风湿关节炎患者关节旁骨加速骨吸收的发病机制。首先，我们发现类风湿关节炎患者的骨髓与小鼠胸腺中的哺育细胞几乎具有相同的功能，表现为假性积血。RA患者的骨髓具有与小鼠胸腺出现假性积血的哺育细胞几乎相同的功能。这些细胞。护士样细胞。类风湿性关节炎患者滑膜组织和骨髓通过假性积血支持高度活化的血细胞。正常人CD14(-)外周血单核细胞在共培养的类风湿关节炎患者滑膜组织中获得护士样细胞的支持，并在5周内被激活并分化为TRAP阳性的单核细胞。这些单核…在IL-3、IL-5、IL-7和/或粒细胞-巨噬细胞集落刺激因子的刺激下，更多的耳细胞融合并分化为多核巨细胞。这些多核巨细胞具有在牙本质切片上形成凹坑的能力，提示其具有骨吸收活性，并表达玻璃连结蛋白受体。用免疫细胞化学方法检测碳酸氢酶11的表达。这些多核巨细胞具有在牙本质切片上形成凹坑的能力，提示其具有骨吸收活性。TRAP阳性的单核和多核细胞也表达明胶酶A。RT-PCR和Northern印迹分析明胶酶-9(明胶酶-B)、巨噬细胞金属弹性蛋白-12(MMP12)和MMP14(MT1-MMPmPNA)。免疫细胞化学结果显示，这些MMPs均由TRAP阳性的多核细胞产生。TRAP阳性的单个核细胞也可诱导重新标记的软骨盘释放S。这些结果表明，位于软骨滑膜界面滑膜中的TRAP阳性单个核细胞可产生基质金属蛋白酶-2和基质金属蛋白酶9，在关节软骨破坏中可能起重要作用。TRAP阳性的多核细胞在软骨下骨髓腔内增殖。其中大部分是破骨细胞。与RA患者加速骨吸收密切相关。这两种TRAP阳性细胞在关节破坏中起主要作用，并在关节滑膜组织和骨髓间隙中有丰富的成纤维细胞样细胞支持。从另一方面来说。幼年类风湿性关节炎患侧关节生长板发育迟缓。我们还发现，在胶原性关节炎大鼠的关节炎早期，生长板受到了损伤。生长板的破坏不是一个关节破坏的序列，而是一个独立于关节滑膜炎的事件，并伴随着肥大软骨细胞中基质金属蛋白酶-3和血管内皮生长因子的表达增加。这些发现还表明，骨髓病变参与了关节炎生长板的破坏。较少

项目成果

Takahi K, Ochi T.: "Early closure of growth plate causes poor growth of long bones in collgen induced arthritis rats."J Musculoskel Neuron Interact.. 2(4). 34-351 (2002)

Takahi K, Ochi T.：“生长板过早闭合会导致胶原诱导的关节炎大鼠长骨生长不良。”J Musculoskel Neuron Interact.. 2(4)。

Hirohata S, Tomita T, Ochi T: "Bone marrow CD34^+ progenitor cells stimulated with the stem cell factor and GM-CSF have the capacity to activate lgD-B through direct cellular interaction"J Leukoc Biol. 71(6). 987-995 (2002)

Hirohata S、Tomita T、Ochi T：“用干细胞因子和 GM-CSF 刺激的骨髓 CD34^ 祖细胞具有通过直接细胞相互作用激活 lgD-B 的能力”J Leukoc Biol。

Tomita T, Ochi T, Yoshikawa, H: "Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis"Arthritis Rheum.. 46(2). 373-378 (2002)

Tomita T、Ochi T、Yoshikawa、H：“类风湿性关节炎中细胞外基质金属蛋白酶诱导物的表达和基质金属蛋白酶产生的增强”Arthritis Rheum.. 46(2)。

Takeuchi E, Ochi T: "VLA-4-dependent and-independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients"Arthritis Res. 4(6). R10 (2002)

Takeuchi E、Ochi T：“类风湿性关节炎患者的滑膜护士样细胞在细胞接触诱导的促炎细胞因子产生中的 VLA-4 依赖和独立途径”Arthritis Res。

Tomita T, Ochi T: "Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metaloproteinases in rheumatoid arthritis"Arthritis Rheum. 46(2). 373-378 (2002)

Tomita T、Ochi T：“类风湿性关节炎中细胞外基质金属蛋白酶诱导物的表达和基质金属蛋白酶产生的增强”关节炎大黄。