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过程中起重要作用，我们探讨了类风湿关节炎滑膜中破骨细胞的发生机制。我们首先检测了白细胞介素-II对类风湿性滑膜成纤维细胞中NF-κB配体受体激活因子（RANKL）表达的影响，RANKL是破骨细胞生成的关键蛋白。通过RT-PCR分析评估，风湿性关节炎滑膜成纤维细胞表达少量RANKL mRNA。IL-11在10 ng/ml浓度下增强RANKL表达。相反，IL-11不影响骨保护素（OPG）的产生，OPG是RANK的诱饵受体。这些结果表明，IL-11可能通过增强类风湿滑膜细胞中RANKL的表达而参与类风湿滑膜中破骨细胞的生成。我们接下来检查了滑膜T细胞对类风湿性滑膜中破骨细胞生成的影响，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细胞的共培养导致抗酒石酸酸性磷酸酶（TRAP）阳性多核巨细胞（TRAP-MGCs）的产生，RANKL介导的信号可能部分参与TRAP-MGCs的产生。虽然产生的TRAP-MGCs不能再吸收牙本质，但这些细胞可能具有分化为破骨细胞的能力。这些发现为类风湿性关节炎滑膜中破骨细胞的发生提供了新的认识。

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.