Chitosan vector system is expected to be useful for direct gene therapy for joint disease. This study first sought to confirm that foreign genes can be transferred to articular chondrocytes in primary culture. Next, chitosan-DNA nanoparticles containing IL-IRa or IL-10 gene were injected directly into the knee joint cavities of osteoarthritis rabbits to clarify the in vivo transfer availability of the chitosan vectors. Clear expression of IL-IRa was detected in the knee joint synovial fluid of the chitosan IL-1Ra-injected group. While no expression was detected in the chitosan IL-10-injected group, this demonstrates that the transfection efficiency of chitosan-DNA nanoparticles was closely related to the type of the gene product. A significant reduction was also noted in the severity of histologic cartilage lesions in the group that received the chitosan IL-1Ra injection. This avenue may therefore represent a promising future treatment for osteoarthritis. (c) 2006 Elsevier Inc. All rights reserved.