Salo Jari, Mackiewicz Zygmunt, Indahl Aage, Konttinen Yrjö T, Holm Allison Kaigle, Sukura Antti, Holm Sten
Department of Orthopedic Surgery, Helsinki University Central Hospital, Finland.
Spine (Phila Pa 1976). 2008 Apr 15;33(8):839-44. doi: 10.1097/BRS.0b013e31816b1f1d.
Proteinases were immunohistochemically stained to analyze degenerated discs and paradiscal tissues in comparison to contiguous control tissues in an experimental porcine model of intervertebral disc degeneration.
The aim was to analyze plasmin and metalloproteinases known to participate in mutual activation cascades.
Comparison of the degenerated discs and paradiscal structures with control tissues disclosed accumulation of plasmin and induction of matrix metalloproteinases (MMP), MMP-1 and MMP-2 in the discs, but some other MMPs in reactive and remodeling tissues.
In 6 domestic pigs, the cranial L4 endplate was perforated to penetrate the nucleus pulposus. Three months later, the animals were killed and the experimental and the contiguous control vertebrae, complete with their intervertebral discs, were excised and subjected to histologic and immunohistochemical examinations.
Immunohistochemical analysis disclosed increased expression of MMP-1 and MMP-2 in the traumatized and degenerated intervertebral discs. Some MMPs were also induced in all paradiscal structures (bone marrow, vertebral bone, and spinal ligaments), or decreased in already scarred areas. The common denominator for all the anatomic sites studied was accumulation of plasmin.
Fibroblast collagenase (MMP-1) and gelatinase A (MMP-2), capable of degrading native and denatured collagen, were induced in degenerating intervertebral discs. Use of an experimental model enabled demonstration that biomechanical destabilization and degeneration of the disc also affects all other paradiscal structures, which are subjected to proteolysis and/or reparative fibrosis apparently representing remodeling of the spine subjected to pathologic stress. Profiling of various MMPs and plasmin, known to participate in mutual activation cascades, suggests that plasmin could activate pro-MMP-1, pro-MMP-2, pro-MMP-3, pro-MMP-7, pro-MMP-9, and pro-MMP-13 and alone or/and in cooperation with MMP-3 initiate at least 2 mutual MMPs activation cascades driven by activated MMP-3 and MMP-7.
在猪椎间盘退变实验模型中，采用免疫组织化学方法对蛋白酶进行染色，以分析退变椎间盘及椎间盘旁组织，并与相邻对照组织进行比较。
分析已知参与相互激活级联反应的纤溶酶和金属蛋白酶。
将退变椎间盘及椎间盘旁结构与对照组织进行比较，发现椎间盘内纤溶酶积聚，基质金属蛋白酶（MMP）-1和MMP-2被诱导，而在反应性和重塑组织中一些其他MMPs也有变化。
对6头家猪，在L4椎体上终板打孔穿透髓核。3个月后处死动物，切除实验椎体及相邻对照椎体及其椎间盘，进行组织学和免疫组织化学检查。
免疫组织化学分析显示，在创伤性退变椎间盘中MMP-1和MMP-2表达增加。在所有椎间盘旁结构（骨髓、椎体骨和脊柱韧带）中一些MMPs也被诱导，或在已形成瘢痕的区域中减少。所有研究解剖部位的共同特征是纤溶酶积聚。
在退变椎间盘中诱导产生了能够降解天然和变性胶原的成纤维细胞胶原酶（MMP-1）和明胶酶A（MMP-2）。使用实验模型能够证明，椎间盘的生物力学不稳定和退变也会影响所有其他椎间盘旁结构，这些结构会发生蛋白水解和/或修复性纤维化，这显然代表了脊柱在病理应力下的重塑。对已知参与相互激活级联反应的各种MMPs和纤溶酶进行分析表明，纤溶酶可激活MMP-1前体、MMP-2前体、MMP-3前体、MMP-7前体、MMP-9前体和MMP-13前体，并单独或与MMP-3协同启动至少2个由活化的MMP-3和MMP-7驱动的相互MMPs激活级联反应。
