The role of interleukin-1 in bone resorption in rheumatoid arthritis
The role of interleukin-1 in bone resorption in rheumatoid arthritis
复制标题
DOI：
10.1093/rheumatology/keh202
复制
发表时间：
2004-06-01
期刊：
影响因子：
5.5
通讯作者：
Kavanaugh, A. F.
中科院分区：
文献类型：
--
作者：
Strand, V.;Kavanaugh, A. F.
RA的骨丢失包括关节旁骨质减少、侵蚀和全身性骨质疏松。在每种情况下，新骨基质的合成不能平衡破骨细胞介导的骨吸收，导致净骨丢失。IL-1、TNF和其他促炎细胞因子刺激破骨细胞分化和活化，导致骨丢失。此外，这些促炎细胞因子刺激滑膜成纤维细胞和软骨细胞产生降解软骨的蛋白酶。在动物关节炎模型中，阻断IL-1可显著减少骨侵蚀和软骨降解，而阻断TNF可减少滑膜炎。在活动性RA患者中，用TNF阻断剂依那西普和英夫利昔单抗以及重组人IL-1受体拮抗剂阿那白滞素治疗，可显著减少侵蚀和关节间隙狭窄。然而，这些生物学疗法是否能减缓放射学进展，显著改善RA的长期预后，仍有待确定。
Bone loss in RA includes juxta-articular osteopenia, erosions and systemic osteoporosis. In each case, synthesis of new bone matrix is unable to balance osteoclast-mediated bone resorption, resulting in net bone loss. IL-1, TNF and other proinflammatory cytokines stimulate osteoclast differentiation and activation, resulting in bone loss. In addition, these proinflammatory cytokines stimulate synovial fibroblasts and chondrocytes to produce proteinases that degrade cartilage. In animal arthritis models, blocking IL-1 significantly reduces bone erosions and cartilage degradation, whereas blocking TNF decreases synovitis. In patients with active RA, treatment with the TNF blockers etanercept and infliximab, as well as with anakinra, a recombinant human IL-1 receptor antagonist, significantly reduced erosions and joint space narrowing. It remains to be determined, however, whether slowing radiographic progression with these biological therapies will significantly improve long-term outcomes in RA.