中文摘要：

像成纤维细胞的 synoviocytes (FLS ) 在风湿性关节炎(RA ) 贡献 synovial 增生。Smoothened (Smo ) 是发信号的声音的刺猬(嘘) 的一个关键部件并且贡献肿瘤房间增长。这研究的目的是在 RA synoviocyte 增长调查 Smo 的角色。FLS 从 RA synovium 被孤立。发信号的嘘用一个 Smo 对手(GDC-0449 ) 和在 FLS 指向 Smo 基因的小介入 RNA (siRNA ) 被学习。房间增长被使用 kit-8 试金和房间周期分发确定， apoptosis 被流动 cytometry 评估。房间周期相关的基因和蛋白质被即时 PCR 和西方的污点检测。与 GDC-0449 或 Smo-siRNA 对待的 FLS 与控制相比显示出显著地减少的增长(P <； 0.05 ) 。有 GDC-0449 的孵化或有 Smo-siRNA 的 transfection 与控制相比导致了 G ₁ 阶段房间的重要增加(P <； 0.05 ) 。房间周期拘捕被 cyclin D1 和 E1 mRNA 表示的重要增加验证，在在 Smo-siRNA transfected 房间的 cyclin 依赖的 kinase p21 mRNA 表示的减少(P <； 0.05 ) 。cyclin D1 的蛋白质表示也是在 Smo 基因以后的 downregulated 击倒(P <； 0.05 ) 。结果建议发信号的嘘以一种 Smo 依赖的方式在 RA-FLSs 增长起一个重要作用并且可以贡献 synovial 增生。指向嘘发信号可以帮助与 RA 在病人控制联合损坏。

英文摘要：

Fibroblast-like synoviocytes （FLSs） contribute to synovial hyperplasia in rheumatoid arthritis （RA）. Smoothened （Smo） is a key component of sonic hedgehog （Shh） signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist （GDC-0449） and small interfering RNA （siRNA） targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls （P〈0.05）. Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls （P 〈 0.05）. Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells （P 〈 0.05）. Protein expression of cyclin D1 was also downregulated after Smo gene knockdown （P 〈0.05）.The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.