Effects of AAV2-mediated co-transfection of CTGF and TIMP1 genes on degenerative lumbar intervertebral discs in rhesus monkeys in vivo

American Journal of Translational Research

Jie Kong¹  Yong Liu² 

[1] Department of Orthopedic Surgery, Rushan city Hospital, 128 Shengli Street, Rushan, Shandong, China;Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, 16 Jiangsu Street, Qingdao, Shandong, China

关键词: Adeno-associated virus;    connective tissue growth factor;    tissue inhibitor of metalloproteinases 1;    rhesus monkey;    intervertebral discs;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Objective: This study aims to investigate the effects of co-transfection of the genes for connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP1) mediated by adeno-associated virus 2 (AAV2) on degenerative lumbar intervertebral discs in a primate model. Methods: Twelve 4-7 year-old rhesus monkeys weighing 4.5-7.0 kg were utilized. CTGF and TIMP1 genes carried by AAV2 were injected into the degenerative lumbar intervertebral discs. Cytokine expression and biological effects were determined using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and 35S-sulfate incorporation assays. A rhesus monkey model of intervertebral disc degeneration was successfully established. Results: At post-transfection, CTGF mRNA expression was higher in the transfection group than in the control group (P < 0.05). Furthermore, TIMP1 mRNA expression in the transfection group was several times the levels observed in the control group (P < 0.05). Moreover, type-II collagen mRNA expression was higher in the transfection group than in the control group (P < 0.05). In addition, higher aggrecan mRNA expression and synthesis were observed in the transfection group, compared to that in the control group (P < 0.05). Conclusion: The stable expression of CTGF and TIMP1 genes in vivo promoted the synthesis of aggrecan and type II collagen in the nucleus pulposus in the rhesus monkey model of intervertebral disc degeneration, which has a potential for intervertebral disc regeneration.

【 授权许可】

CC BY-NC