The role of interleukin 11 in bone resorption by rheumatoid synovial cells

炎性骨吸收是类风湿关节炎(RA)关节破坏的重要因素。由于破骨细胞在骨吸收中起重要作用，我们对类风湿滑膜中破骨细胞的形成机制进行了研究。我们首先检测了IL-11对类风湿滑膜成纤维细胞中破骨细胞形成的关键蛋白--核因子受体激活剂κB配体(RANKL)表达的影响。RT-PCR分析表明，类风湿滑膜成纤维细胞表达少量RANKL mRNA。IL-11在10 ng/ml浓度下促进RANKL的表达，但不影响RANK的诱骗受体--护骨素(OPG)的产生。提示IL-11可能通过增强类风湿滑膜细胞RANKL的表达而参与类风湿滑膜破骨细胞的形成。我们接下来研究了滑膜T细胞在类风湿滑膜破骨细胞形成中的作用，因为已知滑膜T细胞强烈表达RANKL蛋白。我们发现，滑膜巨噬细胞和滑膜T细胞共培养可产生抗酒石酸酸性磷酸酶(TRAP)阳性的多核巨细胞(TRAP-mGCS)，RANKL介导的信号转导可能部分参与了TRAP-mGCS的产生。尽管生成的TRAP-mGCS不能吸收牙本质，但这些细胞很可能具有向破骨细胞分化的能力。这些发现为类风湿滑膜中破骨细胞的发生提供了新的见解。

Inflammatory bone resorption is an important factor for joint destruction of rheumatoid arthritis (RA). Since osteoclasts play important roles in the bone resorption, we examined about the mechanism of osteoclastogenesis in rheumatoid synovium. We first examined the effect of interleukin-ll on the expression of receptor activator of NF-_κB ligand (RANKL), which is a critical protein for osteoclastogenesis, in rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts expressed small amounts of RANKL mRNA, as assessed by RT-PCR analysis. IL-11 enhanced the RANKL expression at a concentration of 10 ng/ml. In contrast, IL-11 did not affect the production of osteoprotegerin (OPG), a decoy receptor for RANK. These results suggested that IL-11 might be involved in osteoclastogenesis in rheumatoid synovium via enhanced expression of RANKL in rheumatoid synovial cells. We next examined the effect of synovial T cells on osteoclastogenesis in rheumatoid synovium because synovial T cells are known to strongly express RANKL protein. We found that the co-culture of synovial macrophages and synovial T cells resulted in the generation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated giant cells (TRAP-MGCs), and that RANKL-mediated signaling may be partially involved in the generation of TRAP-MGCs. Although the generated TRAP-MGCs could not resorb a dentine, it is likely that these cells have the ability to differentiate to osteoclast. These findings provide new insights in the osteoclastogenesis in rheumatoid synovium.