TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis
TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis
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DOI：
10.1016/s0002-9440(10)63016-7
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发表时间：
2001-11-01
影响因子：
6
通讯作者：
Gravallese, EM
中科院分区：
文献类型：
--
作者：
Pettit, AR;Ji, H;Gravallese, EM
有相当多的证据表明，破骨细胞参与了类风湿性关节炎局灶性骨侵蚀的发病机制。肿瘤坏死因子相关激活诱导的细胞因子，也称为核因子-κ β配体受体激活因子（TRANCE/ RANKL），是破骨细胞分化的必需因子。除了在破骨细胞分化和活化中的作用外，TRANCE/RANKL还具有增强T细胞树突状细胞协同相互作用的功能。为了进一步评价破骨细胞在关节炎局灶性骨侵蚀中的作用，我们使用绕过T细胞活化要求的血清转移模型在TRANCE/RANKL敲除小鼠中产生炎性关节炎。这些动物表现出以缺乏破骨细胞为特征的骨硬化表型。通过关节炎临床体征和组织病理学评分测量的炎症在野生型和TRANCE/ RANKL敲除小鼠中相当。显微计算机断层扫描和组织病理学分析表明，与对照同窝小鼠相比，TRANCE/RANKL敲除小鼠的骨侵蚀程度显著降低。相反，在对照同窝小鼠和TRANCE/RANKL敲除小鼠中均存在软骨侵蚀。这些结果证实了破骨细胞在关节炎骨侵蚀发病机制中的核心作用，并证明了这种关节炎动物模型中软骨破坏和骨侵蚀的不同机制。
There is considerable evidence that osteoclasts are involved in the pathogenesis of focal bone erosion in rheumatoid arthritis. Tumor necrosis factor-related activation-induced cytokine, also known as receptor activator of nuclear factor-kappa beta ligand (TRANCE/ RANKL) is an essential factor for osteoclast differentiation. In addition to its role in osteoclast differentiation and activation, TRANCE/RANKL also functions to augment T-cell dendritic cell cooperative interactions. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, we generated inflammatory arthritis in the TRANCE/RANKL knockout mouse using a serum transfer model that bypasses the requirement for T-cell activation. These animals exhibit an osteopetrotic phenotype characterized by the absence of osteoclasts. Inflammation, measured by clinical signs of arthritis and histopathological scoring, was comparable in wild-type and TRANCE/ RANKL knockout mice. Microcomputed tomography and histopathological analysis demonstrated that the degree of bone erosion in TRANCE/RANKL knockout mice was dramatically reduced compared to that seen in control littermate mice. in contrast, cartilage erosion was present in both control littermate and TRANCE/RANKL knockout mice. These results confirm the central role of osteoclasts in the pathogenesis of bone erosion in arthritis and demonstrate distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis.