Gene Therapy of Rheumatoid Arthritis

受类风湿性关节炎（RA）影响的滑膜的特征在于滑膜增生，其导致不可逆的软骨和骨破坏。目前和实验性治疗的目的主要是纠正潜在的免疫异常，但这些治疗往往证明在防止侵入性破坏无效。我们研究了细胞周期蛋白依赖性激酶抑制剂在类风湿性滑膜细胞中的表达，作为抑制滑膜细胞增殖的一种手段。结果表明，来自肥大滑膜的滑膜细胞在其生长受到抑制时容易表达p16TNK4A。但这不是。在其他类型的成纤维细胞中观察到。使用plGINK 4A基因的体内腺病毒基因治疗有效地抑制了RA动物模型的病理。这些观察表明，pl6 TNK 4A的诱导可能为RA的有效治疗提供了一种新的方法。

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.