Establishment of a Rat Model that Recapitulates the Spectrum of Human Intervertebral Disc Degeneration Provisionally Accepted

Bin Zhang¹ Peng Peng^1* Ping Hu¹ Wenxiang Li¹ Jiangang Cao² Liang Liu³ Shiqing Feng^1*

• ¹Tianjin Medical University General Hospital, China
• ²Tianjin Hospital, Tianjin University, China
• ³Beijing Luhe Hospital, Capital Medical University, China

Our study aims to establish a rat model that mimics the native pathogenesis of human intervertebral disc degeneration (IDD) by combining decompression instability of lumbar vertebrae with upright posture. The Wistar rats were divided into four groups: sham, sham-upright, instability, and instability-upright group. Instability was induced by resection of facet joints, supra-and inter-spinous, and yellow ligaments, spinous process, vertebral laminae at L2-L3 levels. Besides, the upright position was held by a fixation machine for eight hours throughout 12 weeks. The degeneration of discs was assessed via pain behaviour assessment and micro-computed tomography (micro-CT), magnetic resonance imaging (MRI), histological analysis, immunofluorescence, and quantitative real-time PCR (qRT-PCR). Compared with the sham group, instability and instability-upright groups showed lower pain threshold, progressive disc height narrowing and decreased T2 values. Consistent with increased histological scores, immunofluorescence displayed the decrease of aggrecan and type II collagen (Col II). Moreover, qRT-PCR showed upregulated expression of MMP13 and ADMAST-5. Given the essential role of excessive mechanical loading in the pathogenesis of human disc degeneration, instability-upright not only successfully reproduced IDD but also accelerated and aggravated the disc degeneration of this model.