In vivo experimental intervertebral disc degeneration induced by bleomycin in the rhesus monkey

BMC Musculoskeletal Disorders

Shaoyu Liu²  Wenfang Chen¹  Haixing Sun³  Manman Gao²  Xuenong Zou²  Shangbin Cui²  Ximin Pan³  Le Wang²  Zhiyu Zhou⁴  Rui Zhong²  Fuxin Wei² 

[1] Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Department of Spine Surgery, the First Affiliated Hospital and Orthopedic Research Institute of Sun Yat-sen University, Guangzhou, China;Department of Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;The medical school of Shenzhen University, Shenzhen, China

关键词: Rhesus monkey;    Magnetic resonance imaging;    Animal model;    Bleomycin;    Intervertebral disc degeneration;   

Others  :  1121972
DOI  :  10.1186/1471-2474-15-340

 received in 2014-06-15, accepted in 2014-10-03,  发布年份 2014

【 摘 要 】

Background

Recently, biological therapies for early intervention of degenerative disc disease have been introduced and developed; however, a functional animal model that mimics slowly progressive disc degeneration of humans does not exist. The objective of this study was to establish a slowly progressive and reproducible intervertebral disc (IVD) degeneration model.

Methods

The subchondral bone adjacent to the lumbar IVDs (L3/4 and L5/6) of ten rhesus monkeys was randomly injected with 4 ml bleomycin solution (1.5 mg/ml), or 4 ml phosphate buffer saline (PBS) per segment as control, respectively. The degenerative process was investigated by using radiography and T1ρ MR imaging at 1, 3, 6, 9, 12 and 15 months postoperatively. Histological scoring, Sulfated Glycosaminoglycans (GAGs) analysis and real-time PCR were performed at 15 months. The correlation between histological score, GAGs and T1ρ values were also analyzed.

Results

The results showed that the mean T1ρ values of nucleus pulposus (NP) and annulus fibrosus (AF) in the bleomycin group significantly decreased after 3 and 6 months respectively, followed by slowly decrease until at 15 months. At 15 months, the histological scores was significantly higher, and the GAGs of NP was significantly lower in the bleomycin group, compared with the control group (P < 0.05). The results of real-time PCR revealed a significant increase in matrix metalloprotease (MMP)-3, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, tumor necrosis factor α, interleukin-1β, interleukin-6 expressions, transforming growth factor (TGF-β1) and marked reduction in aggrecan, type II collagen, von willebrand factor (vWF) expressions at the mRNA levels in the bleomycin group. Spearman correlation analysis showed a strong positive correlation between GAGs and T1ρ values of NP (r =0.740, P < 0.01), and a significant inverse correlation between histological score and T1ρ values of NP and AF (r = -0.761, r = -0.729, respectively, P < 0.01).

Conclusions

Injection of bleomycin into the subchondral bone adjacent to the lumbar IVDs of rhesus monkeys can results in mild, slowly progressive disc degeneration, which mimics the onset of human disc degeneration. T1ρ MR imaging is an effective and noninvasive technique for assessment of early stage disc degeneration.

【 授权许可】

   
2014 Wei et al.; licensee BioMed Central Ltd.

【 图 表 】

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