Gene transfer therapy trial of Chondromodulin I for the experimental arthritis

分别于第0、7、14、21天在Lewis大鼠双足部注射丁酸乳杆菌，右膝关节注射1 × 10^<10>pfu病毒，左膝关节注射β-半乳糖苷酶重组腺病毒AxCALacZ。在另一只花药大鼠中注射PBS作为基础对照。每天观察大鼠的关节炎发病情况，并通过对每个膝关节的严重程度和滑膜炎进行分级得出关节炎指数。第10 ~ 14天观察膝关节关节炎。关节炎进展后体重下降。免疫组化染色在注射后的膝关节滑膜组织中发现AxCALacZ。膝关节内注射未见肝损伤，免疫组化染色检查。与注射AxCALacZ的大鼠相比，AxCAChM-I抑制了疾病的进展。AxCAChM-I组滑膜血管数量少于AxCALacZ组。但PBS治疗的滑膜血管数量少于AxCAChM-I治疗。这是由腺病毒载体的免疫原性引起的。软骨调节素基因治疗可能是治疗类风湿性关节炎的有效方法之一，但我们必须改变腺病毒给药方式来治疗软骨调节素。

Lewis rats were injected at their both footpads with M.Butyricum(day 0). 1x10^<10>pfu virus of AxCAChM-I(Chondronodulin I recombinant Adenovirus) was injected in right knee joint and AxCALacZ(β-galactosidase recombinant Adenovirus) were injected in left knee joint at day 0,7,14,and 21. PBS was injected as same protocol in anther rats for basal control. Rats were observed daily for the onset of the arthritis, and an arthritic index was derived by grading the severity and synovitis of each knee joint.The arthritis of knee joint was observed from day 10 to day 14. The body weight was decreased after arthritis progression.AxCALacZ was presented in synovial tissue in injected knee joint by immnohistochemical staining. No liver injury was observed by injection into knee joint, which was also checked by immunohistochemical staining.Progression of disease was suppressed by AxCAChM-I compared with AxCALacZ injected rats. The number of blood vessels in synovium treated with AxCAChM-I was less than treated with AxCALacZ. But the number of vessels in synovium treated with PBS was less than treated with AxCAChM-I. This is caused by immunogenicity of adenovirus vector.Gene therapy with Chondronodulin I may be one of the useful methods for rheumatoid arthritis, but we have to change the adenoviral delivery methods for Chondronodulin I treatment.