Fundamental Approach to Gene Therapy for Osteoarthritis

转化生长因子-b是一种强大的多潜能的软骨细胞活性调节因子，在软骨组织的修复中发挥重要作用。通过基因转移将TGT-b转移到关节间隙提供了一种潜在的治疗方式。为了确定利用大鼠作为基因转移系统的可行性，进行了大鼠膝关节内注射。用脂质体将PSV-b半乳糖苷酶载体注射到关节内，以确定这种方法是否有可能进行基因传递。组织学检查滑膜和软骨组织中Lac-z的表达。在这些组织中观察到高效表达。我们还检测了转化生长因子-b在软骨细胞中的信号转导，发现它与其他细胞不同。转化生长因子-β上调软骨细胞c-fos基因的表达。我们现在正在用CAT法检测c-fos基因对转化生长因子-b的反应元件。虽然转化生长因子-b的传递还没有成功，但这些结果表明骨关节炎的基因治疗是可行的。

Transforming growth factor (TGF-b) has been found to be a powerful multipotential regulator of the cellular activity of chondrocytes, and it is assumed to play a role in the repair of cartilage tissue. Delivery of TGT-b to the articular space by gene transfer offers a potential therapeutic modality. To determine the feasibility of using rat as a gene transfer system, intraarticular injections of the rat knee were performed. The pSV-b Galactosidase vector was injected intraarticulaly using lipofectin to ascertain whether gene delivery was possible with this approach. Synovial membrane and cartilage tissue were examined for lac-z expression histologically. High efficiency expression was observed in these tissues. And transgene expression could still be detected after 14 days.We also examined the signal transduction of TGF-b in chondrocytes and found that it was different from the other cells. TGF-b upregulated the induction of c-fos gene in chondrocytes. We are now determing the response element of c-fos gene for TGF-b by using a CAT assay method.Although, the delivery of TGF-b has not been successful, these results suggest the feasibility of gene therapy for osteoarthritis.