Abstract
BackgroundMMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. In this study the hypothesis that increased expression of MMP28 correlates with higher grades of degeneration and is stimulated by the presence of proinflammatory molecules was tested. Gene expression levels of MMP28 were investigated in traumatic and degenerative human IVD tissue and correlated to the type of disease and the degree of degeneration (Thompson grade). Quantification of MMP28 gene expression in human IVD tissue or in isolated cells after stimulation with the inflammatory mediators lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α or the histondeacetylase inhibitor trichostatin A was performed by real-time RT PCR.ResultsWhile MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration.ConclusionsOur results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc.
Highlights
MMP28 is a recently discovered member of the matrix metalloproteinase (MMP) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue
MMP28 expression seemed to be increased in osteoarthritis and degenerated IVD compared to healthy tissue, indicating that it may play an important role during these disease processes [18,19,20,21]
MMP28 gene expression pattern in human disc tissue Analysis of MMP28 gene expression in disc biopsies, which was grouped according to the degree of IVD degeneration (Thompson grade), is shown in Figure 1a: MMP28 was expressed in most of the analyzed disc samples and higher expression levels were found in samples removed because of spine trauma (Thomson grade II = normal adult discs with no disc degeneration)
Summary
MMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. During intervertebral disc (IVD) degeneration, the expression and activity of a number of MMPs is increased, including MMPs 1, 3, 7, 9 and 13 [1] Proinflammatory cytokines such as IL-1b and TNF-a as well as bacterial endotoxins (e.g. lipopolysaccharide LPS). MMP28 is strongly expressed in testis, as well as in bone, kidneys, lung, heart, colon, intestines, brain, skin and carcinomas [12,13,14,15,16,17] It is expressed in cartilage, synovium and IVDs, with lower expression in bovine discs compared to bovine cartilage [18,19,20,21,22]. MMP28 expression seemed to be increased in osteoarthritis and degenerated IVD compared to healthy tissue, indicating that it may play an important role during these disease processes [18,19,20,21]
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