Alterations in biochemical components of extracellular matrix in intervertebral disc herniation: role of MMP-2 and TIMP-2 in type II collagen loss

Abstract

Alterations in the composition of intervertebral disc extracellular matrix, mainly collagen and proteoglycans, may cause changes in mechanical properties of the disc, leading to dysfunction, nerve root compression, and herniation with severe clinical manifestations. Matrix metalloproteinases may be involved in degradation by hydrolysing extracellular matrix components. Inhibitors of matrix metalloproteinases, in contrast, function in the maintenance of degradation control. In this study, we investigated: (i) whether the level of matrix degradation correlated with the duration of the symptomatic disease, (ii) roles of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) in intervertebral disc degeneration. Nucleus pulposus of intervertebral discs were obtained from 22 patients and analysed for collagen and proteoglycan contents, and pro-MMP-2, TIMP-2 levels. Collagen content was determined as hydroxyproline and proteoglycan content was measured as glycosaminoglycans. The loss in matrix components did not correlate with the duration of the degenerative disc disease. Pro-MMP-2 levels were higher at early stages of the degenerative disc disease (r = -0.495, P < 0.05). TIMP-2 levels were similar in all samples. Pro-MMP-2 and TIMP-2 levels negatively correlated in herniated discs samples (r = -0.855, P < 0.01). Pro- MMP-2 levels negatively correlated with the collagen content in herniated disc material. Our findings may suggest a silent period of active disease prior to symptomatic outcome during which irreversible matrix loss occurs. Involvement of other proteolytic enzymes at different stages of the disease should also be investigated to help to control the degradation cascade at relatively early stages of disc degeneration before the clinical onset of disease.

Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults

“…Enhanced expression of MMP-2 has been found in aging and degenerative discs [3,15,23], and MMP-2 production appears to increase when disc cells are exposed to abnormal physical stresses [5].Furthermore, in situ zymography confirmed that gelatinolytic activity was localized in area close to tissue clefts where MMP-2 was expressed at elevated levels [23]. In addition, Kozaci et al reported that Pro-MMP-2 levels were higher at early stages of the degenerative disc disease, which were negatively correlated with the collagen content in herniated disc material [10].…”

The elastic fibre network of the human lumbar anulus fibrosus: architecture, mechanical function and potential role in the progression of intervertebral disc degeneration

“…MMP-7 expression by cells of the nucleus and inner anulus has been demonstrated, more so for degenerate discs and those having suffered prolapse than for non-degenerate discs [35]. MMP-2 has been shown to be present in nucleus material from discs suffering from the early stages of degeneration, and also in the vicinity of nuclear clefts and anular tears in degenerate discs [34,70]. MMP-9 has been found to be expressed only at very low levels [70].…”

Altered expression of metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in cervical disc herniation patients

“…Additionally, MMPs are capable of breaking down certain ECM proteins and thus have an active impact on ECM remodeling via the degradation of matrix scaffold macromolecules (Nissi et al, 2013). MMP-2 belongs to the MMP family, and plays an important role in ECM degradation both directly and indirectly (Kozaci et al, 2006). It is well known that water and collagen are the major components of the IVD, while the ECM of the NP and AF is mainly composed of type 2 collagens (Yurube et al, 2012;Vo et al, 2013).…”

“…As one important member of the MMP family, MMP-2 actively functions in the secondary breakdown of collagen during the tissue remodeling process (Kozaci et al, 2006;Séguin et al, 2008). Additionally, a large amount of evidence in animal models suggest that MMP-2 is significantly correlated with degenerative changes (Hsieh et al, 2009;Rastogi et al, 2013).…”

“…Particularly, the knockdown of MMP-2 in AF cells leads to a significantly decreased ability to reorganize and contract collagen gels (Rastogi et al, 2013). IVD tissue structure is thought to be mainly composed of collagens and proteoglycans (Kozaci et al, 2006). In the AF, matrix changes are accelerated with increase in age, which is thought to be a result of enhanced catabolic processing of the ECM (Akeda et al, 2007;Salo et al, 2008).…”