Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney, The Royal North Shore Hospital of Sydney, St Leonards, New South Wales, Australia.
Spine (Phila Pa 1976). 2012 Jan 1;37(1):18-25. doi: 10.1097/BRS.0b013e31820cd8d5.
An investigation of mechanical destabilization of the lumbar ovine intervertebral disc (IVD) inducing IVD degeneration (IVDD) as determined by multiparameter outcome measures (magnetic resonance imaging [MRI], IVD composition, biomechanical testing, gene profiling, immunohistochemistry, and immunoblotting).
To assess the effect of IVD mechanical destabilization on matrix protein and metalloproteinase gene expression to investigate the pathophysiological mechanisms of lumbar IVDD.
Several earlier studies have used annular transection to induce IVDD in sheep, but none have optimized or validated the most appropriate lesion size.
The annulus fibrosus (AF) incision inducing maximal change in IVD biomechanics was applied to L1-L2, L3-L4, and L5-L6 discs in vivo to compare with a sham procedure at 3 months post operation. IVDs were evaluated by MRI, biomechanics, histopathology, proteoglycan and collagen content, gene expression, and aggrecan proteolysis by Western blotting.
Significant changes were observed in lesion (6 × 20 mm(2)) compared with sham IVDs at 3 months post operation: reduced disc height on MRI; increased neutral zone in biomechanical testing; depleted proteoglycan and collagen content in the nucleus pulposus (NP) and lesion half of the AF but not in the contralateral AF; increased messenger RNA for collagen I and II, aggrecan, versican, perlecan, matrix metalloproteinase (MMP)-1 & 13, and ADAMTS-5, in the lesion-site AF and NP but not in the contralateral AF. ADAMTS-4 messenger RNA was increased in the lesion-site AF but decreased in the NP. Despite an upregulation in MMPs, there was no change in MMP- or ADAMTS-generated aggrecan neoepitopes in any region of the IVD in lesion or sham discs.
Lumbar IVDD was reproducibly induced with a 6 × 20 mm(2) annular lesion, with focal dysregulation of MMP gene expression, cell cloning in the inner AF, loss of NP aggrecan, and disc height. Loss of aggrecan from the NP was not attributable to increased proteolysis in the interglobular domain by MMPs or ADAMTS.
通过多参数结果测量（磁共振成像[MRI]、椎间盘成分、生物力学测试、基因谱分析、免疫组织化学和免疫印迹），研究腰椎椎间盘中的机械不稳定性（IVD）导致椎间盘退变（IVDD）的情况。
评估 IVD 机械不稳定对基质蛋白和金属蛋白酶基因表达的影响，以探讨腰椎 IVDD 的病理生理机制。
一些早期的研究已经使用环形切开术在绵羊中诱导 IVDD，但没有一项研究优化或验证了最合适的病变大小。
将纤维环（AF）切开术应用于 L1-L2、L3-L4 和 L5-L6 椎间盘，以最大程度地改变 IVD 生物力学特性，与术后 3 个月的假手术进行比较。通过 MRI、生物力学、组织病理学、糖胺聚糖和胶原蛋白含量、基因表达以及 Western 印迹分析 aggrecan 蛋白水解来评估 IVD。
与 sham IVD 相比，术后 3 个月时病变（6×20mm²）观察到显著变化：MRI 上椎间盘高度降低；生物力学测试中中性区增加；NP 和病变半侧 AF 中的糖胺聚糖和胶原蛋白含量减少，但对侧 AF 中无变化；病变侧 AF 和 NP 中的胶原 I 和 II、aggrecan、versican、perlecan、基质金属蛋白酶（MMP）-1 和-13、ADAMTS-5 的信使 RNA 增加，但对侧 AF 中无变化。病变侧 AF 中的 ADAMTS-4 信使 RNA 增加，而 NP 中的减少。尽管 MMP 表达上调，但在病变或 sham 椎间盘的 IVD 任何区域均未观察到 MMP 或 ADAMTS 产生的 aggrecan 新表位的变化。
使用 6×20mm²环形病变可重复性地诱导腰椎 IVDD，伴有 MMP 基因表达的局灶性失调、内 AF 中的细胞克隆、NP aggrecan 丢失和椎间盘高度降低。NP 中 aggrecan 的丢失不能归因于 MMP 或 ADAMTS 对 interglobular 结构域的蛋白水解作用增加。
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