Direct chitosan-mediated gene delivery to the rabbit knee joints in vitro and in vivo.
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-1Ra 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-1Ra 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.
Zhang
Xiaoling
X
Institute of Health Sciences, Shanghai Jiao Tong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, PR China. xlzhang@sibs.ac.cn
Yu
Changlong
C
Xushi
Zhang
Chao
C
Tang
Tingting
T
Dai
Kerong
K
D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D019902:Chondrocytes / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D007719:Knee Joint / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000628:therapy*; D011817:Rabbits; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome
D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D016753:Interleukin-10; D004247:DNA; D048271:Chitosan