Gene Therapy of Rheumatoid Arthritis

类风湿关节炎（RA）影响的滑膜的特点是滑膜增生导致不可逆的软骨和骨破坏。目前的和实验性的治疗主要是为了纠正潜在的免疫异常，但这些治疗往往被证明在防止侵入性破坏方面是无效的。我们研究了细胞周期蛋白依赖性激酶抑制剂在类风湿滑膜细胞中的表达，作为抑制滑膜细胞增殖的一种手段。结果表明，增生滑膜衍生的滑膜细胞在生长受到抑制时容易表达pl6TNK4A。但事实并非如此。在其他类型的成纤维细胞中观察到。plGINK4A基因在体内腺病毒基因治疗能有效抑制RA动物模型的病理变化。这些观察结果表明，诱导pl6TNK4A可能为有效治疗RA提供了一种新的途径。

The synovia affected by rheumatoid arthritis (RA) is characterized by synovial proliferation which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed largely at correction of the underlying immune abnormalities, but these treatments often prove ineffective in preventing the invasive destruction. We studied the expression of cyclin dependent kinase inhibitors in rheumatoid synovial cells as a means of suppressing synovial cell proliferation. The results showed that the synoviial cells derived from hypertrophic synovia readily express pl6TNK4A when they were growth-inhibited. This was not. observed in other types of fibroblasts. In vivo adenoviral gene therapy with the plGINK4A gene efficiently inhibited the pathology in an animal model of RA.These observations indicated that the induction of pl6TNK4A may provide a novel approach to the effective treatment of RA.