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.

我们已经证明了骨髓病变在类风湿关节炎患者的关节破坏中的参与。我们在体外发现了这些TRAP阳性多核细胞的生成过程。这可能与RA患者关节旁骨吸收加速的发病机制有关。首先，我们发现RA患者的骨髓与小鼠胸腺的护士细胞具有几乎相同的功能，而护士细胞在小鼠胸腺中表现出假经验沉积。类风湿关节炎患者的骨髓与小鼠胸腺中出现假经验沉积的护士细胞具有几乎相同的功能。这些细胞。Nurse-like细胞。RA患者的滑膜组织和骨髓通过假经验沉积支持高度活化的血细胞。来自健康个体的CD14（-）外周血单核细胞与来自RA患者滑膜组织的护士样细胞共培养，并在培养5周内激活并分化为TRAP阳性的单核细胞。这些单核细胞在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，表明其具有骨吸收活性并表达玻璃体粘连蛋白受体。和碳酸酐酶11通过免疫细胞化学。这些多核巨细胞具有在牙本质切片上形成凹坑的能力，表明其具有骨吸收活性。这些TRAP（+）单核和多核细胞也表达MMP-2（明胶酶- a）。MMP-9 (gelatinase-B)。RT-PCR和northern blot分析巨噬细胞金属弹性蛋白酶（MMP-12）和巨噬细胞金属弹性蛋白酶（MMP-14）的mPNA。免疫细胞化学结果显示，MMP-2、MMP-9和MMP-14是由TRAP阳性的多核细胞产生的。TRAP阳性的单核细胞也诱导从重新标记的软骨椎间盘释放S^<35>。这些结果表明，位于软骨滑膜界面处的滑膜上的trap阳性单核细胞产生MMP-2和mmp - 9，并在关节软骨破坏中发挥重要作用。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患者骨吸收加速密切相关。这两种trap阳性细胞在关节破坏中起主要作用，并得到关节和骨髓间隙滑膜组织中大量成纤维细胞样细胞的支持。另一方面。幼年类风湿性关节炎患关节附近生长板发育迟缓。我们还发现胶原诱导关节炎大鼠的生长板在关节炎早期受到损伤。生长板的破坏不是关节破坏的序列，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MMP-3和VGEF的表达增加。这些发现也表明骨髓损伤参与关节炎生长板的破坏。少

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