TITLE:
Inhibition of Osteoarthritis in Rats by Electroporation with Interleukin-1 Receptor Antagonist
AUTHORS:
Zhen Sun, Heyong Yin, Xiaoming Yu, Xun Sun, Bo Xiao, Yichi Xu, Zhiguo Yuan, Haoye Meng, Jiang Peng, Changlong Yu, Yu Wang, Quanyi Guo, Aiyuan Wang, Shibi Lu
KEYWORDS:
Electroporation, Interleukin-1 Receptor Antagonist, Adeno-Associated Virus, Gene Therapy, Osteoarthritis, Cartilage, Synovium
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.9 No.7,
June
15,
2016
ABSTRACT: Gene therapy constitutes a promising strategy for the treatment of osteoarthritis (OA). We assessed the use of electroporation (EP) of non-viral gene vectors, and compared its efficacy with that of adeno-associated virus (AAV) vectors. EP- and AAV-mediated delivery of human interleukin-1 receptor antagonist (hIL-1Ra) was localized performed in the joints of rats following induction of OA. mRNA levels for hIL-1Ra, IL-1β, TNF-α, MMP-13 and ADAMTS-4 in the cartilage and synovial tissues were analyzed. Structural analyses of the subchondral bone at the medial femoral condyle were performed by Micro-CT after treatment. Knee joint specimens were staining with hematoxylin and eosin and Saffron O. Induction of hIL-1Ra by both EP and AAV inhibited inflammatory-induced sub-chondral bone reconstruction, and effectively suppressed IL-1β activity, as evidenced by decreased expression of MMP-13 and ADAMTS-4. Histological analyses revealed significant protection of cartilage, proteoglycan by EP and AAV. hIL-1Ra expression was similar in both the EP and AAV groups. Notably, this gene is not easier degraded transduced by EP compared with AAV. Taken together, these results show that EP offers transfection efficiency comparable to that of AAV, with the potential for longer gene expression, making EP a promising candidate for efficient non-viral delivery of OA gene therapy.