Rheumatoid and pyrophosphate arthritis synovial fibroblasts induce osteoclastogenesis independently of RANKL, TNF and IL-6.
Rheumatoid and pyrophosphate arthritis synovial fibroblasts induce osteoclastogenesis independently of RANKL, TNF and IL-6.
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DOI：
10.1016/j.jaut.2012.06.001
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发表时间：
2012-12
影响因子：
12.8
通讯作者：
Adamopoulos IE
中科院分区：
文献类型：
--
作者：
Dickerson TJ;Suzuki E;Stanecki C;Shin HS;Qui H;Adamopoulos IE
骨破坏是炎性关节炎的常见特征，并且由破骨细胞介导，破骨细胞是唯一进行骨吸收的专门细胞。破骨细胞分化诱导因子核因子κ β受体激活因子配体（RANKL）的异常表达与类风湿关节炎（RA）的骨病理和滑膜成纤维细胞有关。在这篇文章中，我们挑战了目前的概念，即RANKL表达的增加控制自身免疫性关节炎中的破骨细胞生成和骨破坏。我们从RA、焦磷酸盐关节病（PPA）和骨关节炎（OA）患者中分离人成纤维细胞，并分析其RANKL/OPG表达谱及其分泌因子诱导破骨细胞生成的能力。我们测定了RA成纤维细胞中RANKL mRNA和蛋白质的增加，与PPA和OA患者相比增加了10倍。将健康志愿者外周血单个核细胞（PBMC）在RA、PPA和OA滑膜成纤维细胞条件培养基中培养。通过抗酒石酸酸性磷酸酶（TRAP）、玻连蛋白受体（VNR）、F-肌动蛋白环形成和骨吸收测定来评估破骨细胞分化。在RANKL拮抗剂骨保护素（OPG）存在下，滑膜成纤维细胞条件培养基培养物中TRAP+、VNR+多核细胞能够形成F-肌动蛋白环和腔隙吸收。在不存在巨噬细胞集落刺激因子（M-CSF）的情况下，破骨细胞在这些培养物中没有形成。我们的数据表明，纯滑膜成纤维细胞培养物的条件培养基含有炎症介质，可以诱导破骨细胞形成的人PBMC独立的RANKL。此外，抑制TNF或IL-6通路不足以消除来自关节炎滑膜成纤维细胞的破骨细胞生成信号。总的来说，我们的数据清楚地表明，在炎症性关节炎中存在交替的破骨细胞生成途径，并将滑膜成纤维细胞作为骨和关节破坏的关键调节细胞，这是自身免疫性关节炎的标志。
Bone destruction is a common feature of inflammatory arthritis and is mediated by osteoclasts, the only specialized cells to carry out bone resorption. Aberrant expression of receptor activator of nuclear factor kappa β ligand (RANKL), an inducer of osteoclast differentiation has been linked with bone pathology and the synovial fibroblast in rheumatoid arthritis (RA). In this manuscript, we challenge the current concept that an increase in RANKL expression governs osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis. We determined a 10-fold increase of RANKL mRNA and protein in fibroblasts isolated from RA relative to PPA and OA patients. Peripheral blood mononuclear cells (PBMC) from healthy volunteers were cultured in the presence of RA, PPA and OA synovial fibroblast conditioned medium. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), F-actin ring formation and bone resorption assays. The formation of TRAP+, VNR+ multinucleated cells, capable of F-actin ring formation and lacunar resorption in synovial fibroblast conditioned medium cultures occured in the presence of osteoprotegerin (OPG) a RANKL antagonist. Osteoclasts did not form in these cultures in the absence of macrophage colony stimulating factor (M-CSF). Our data suggest that the conditioned medium of pure synovial fibroblast cultures contain inflammatory mediators that can induce osteoclast formation in human PBMC independently of RANKL. Moreover inhibition of the TNF or IL-6 pathway was not sufficient to abolish osteoclastogenic signals derived from arthritic synovial fibroblasts. Collectively, our data clearly show that alternate osteoclastogenic pathways exist in inflammatory arthritis and place the synovial fibroblast as a key regulatory cell in bone and joint destruction, which is a hallmark of autoimmune arthritis.
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与骨吸收调节有关的破骨细胞功能抗原在生化上与玻染素受体有关。
DOI：
10.1083/jcb.109.4.1817
发表时间：
1989-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Davies J;Warwick J;Totty N;Philp R;Helfrich M;Horton M
通讯作者：
Horton M
DOI：
10.1186/ar109
发表时间：
2000
期刊：
Arthritis research
影响因子：
--
作者：
Kontoyiannis D;Kollias G
通讯作者：
Kollias G
影响因子：
37.8
作者：
Jaffré, F;Callebert, J;Monassier, L
通讯作者：
Monassier, L
DOI：
10.4049/jimmunol.1003986
发表时间：
2011-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Adamopoulos IE;Tessmer M;Chao CC;Adda S;Gorman D;Petro M;Chou CC;Pierce RH;Yao W;Lane NE;Laface D;Bowman EP
通讯作者：
Bowman EP
影响因子：
56.9
作者：
JILKA, RL;HANGOC, G;MANOLAGAS, SC
通讯作者：
MANOLAGAS, SC