Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis
Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis
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DOI：
10.1002/art.20023
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发表时间：
2004-02-01
影响因子：
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通讯作者：
Ozaki, S
中科院分区：
文献类型：
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作者：
Kawabata, D;Tanaka, M;Ozaki, S
Objective.为了阐明卵泡抑素相关蛋白（FRP）/TSC-36/FSTL 1在类风湿关节炎（RA）中的体内功能，我们研究了FRP在小鼠关节炎模型中的作用。用抗Ⅱ型胶原单克隆抗体和脂多糖诱导BALB/c小鼠关节炎。每天腹膜内注射20 μ g重组FRP处理小鼠。通过临床评分和足垫肿胀评估关节炎的发展。在关节炎发作后第21天对受影响的爪进行组织学检查。使用市售的互补DNA（cDNA）阵列比较FRP处理和未处理小鼠中受影响爪的基因表达谱。通过实时定量逆转录聚合酶链反应证实了基因表达的差异。用重组FRP治疗显示关节炎严重程度的显著改善。组织学分析证实了这一发现，并揭示了减轻细胞浸润到滑膜以及软骨损伤。尿脱氧吡啶啉量的显著减少也表明FRP对关节破坏的改善作用。此外，基因表达谱的cDNA阵列分析显示，在FRP治疗的关节炎病变c-fos，ets-2，IL 6，MMP 3和MMP 9基因的表达减少，其中一些被认为是与滑膜炎症和关节破坏。这些来自体内实验的发现表明，FRP可能是治疗炎性关节疾病如RA的关键分子之一。
Objective. To clarify the in vivo function of follistatin-related protein (FRP)/TSC-36/FSTL1 in rheumatoid arthritis (RA), we investigated the roles of FRP in a mouse model of arthritis.Methods. Arthritis was induced in BALB/c mice by injecting anti-type II collagen monoclonal antibody and lipopolysaccharide. Mice were treated with daily intraperitoneal injections of 20 mug of recombinant FRP. Development of arthritis was assessed by the clinical score and footpad swelling. Histologic examination of affected paws was performed on day 21 after the onset of arthritis. The gene expression profiles of affected paws in FRP-treated and untreated mice were compared using commercially available complementary DNA (cDNA) arrays. The difference in gene expression was confirmed by real-time quantitative reverse transcription-polymerase chain reaction.Results. Treatment with recombinant FRP showed significant amelioration of the arthritis severity. Histologic analyses confirmed this finding and revealed the alleviation of cellular infiltration into the synovium as well as cartilage damage. The significant decrease in the amount of urinary deoxypyridinoline also indicated the ameliorative effect of FRP on joint destruction. Moreover, cDNA array analysis of the gene expression profile in FRP-treated arthritic lesions revealed a reduced expression of the c-fos, ets-2, IL6, MMP3, and MMP9 genes, some of which are thought to be associated with synovial inflammation and joint destruction.Conclusion. These findings from in vivo experiments suggest that FRP could be one of the key molecules in the treatment of inflammatory joint diseases such as RA.