Matrix metalloproteinase-3 on ligamentum flavum in degenerative lumbar spondylolisthesis.
ABSTRACT Human ligamentum flavum (LF) was examined for the activity level of matrix metalloproteinase-3 (MMP-3) in degenerative spondylolithesis (DS) patients using immunohistochemistry, Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR), and quantitative real-time PCR.
To investigate the hypothesis that the activity of MMP-3 is elevated in LF of DS patients, which might contribute to DS pathogenesis.
MMP-3 is a proteinase produced by connective tissue cells and is responsible for the degradation and modification of extracellular matrix molecules. MMP-3 activity has been established in articular cartilage, synovial membrane, and intervertebral discs, but not in the LF.
The experimental group consisted of 18 patients with DS and the control group consisted of 18 patients with spinal stenosis (SS) without any instabilities. MMP-3 expression was measured with in situ using immunohistochemistry and both for mRNA and protein levels.
The MMP-3 positive cell ratio in the LF observed in DS patients was substantially higher than in SS patients (P = 0.030). In Western blot, the average optical density (OD) of MMP-3 was higher in LF of DS than of SS (P = 0.028). There was greater MMP-3 expression in DS patients as quantified by RT-PCR (P = 0.004).
Our study shows that MMP-3 expression in the LF of DS patients was significantly higher than in SS patients. Increased MMP-3 expression may be associated with the degenerative changes of LF in DS patients comprising one of the mechanisms of pathogenesis in DS.
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ABSTRACT: Metalloproteinases produced by connective tissue cells may play a key part in the destruction of joints in rheumatoid arthritis. Matrix metalloproteinase 3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen and of activating procollagenase was immunolocalised in hyperplastic synovial lining cells in rheumatoid synovium, but not in the cells of normal synovium. Cells responsible for synthesis of MMP-3 have the phenotype of synovioblasts (B cells) by immunoelectron microscopy, but not of phagocytic synovial macrophages (A cells). Cultured monolayer of rheumatoid synovial cells synthesises MMP-3 only under treatment with macrophage conditioned medium. Immunolocalisation of MMP-3 in rheumatoid synovium and cultured synovial cells was possible when the specimens were treated with a monovalent ionophore, monensin. These results suggest that MMP-3 is synthesised and secreted continuously without storage from hyperplastic synovioblasts stimulated by factor(s) derived from activated macrophages present in the synovium.Annals of the Rheumatic Diseases 09/1989; 48(8):645-53. · 9.11 Impact Factor
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ABSTRACT: To assess its possible role in the pathophysiology of intervertebral disc degeneration, we investigated the production of matrix metalloproteinase-3 (MMP-3) using human intervertebral disc explant culture. Five normal and 10 degenerated disc specimens were used. The levels of MMP-3 released in the medium were measured with use of an enzyme immunoassay. The results showed that the level of MMP-3 in the degenerated group (0.57 microg/ml/mg wet weight; n = 10) was significantly higher than that of the control group (0.29 microg/ml/mg wet weight; n = 5) (p < 0.05). Immunostaining of MMP-3 revealed that the ratio of positive staining cells in the degenerated group was greater than that of the control group. These observations suggest that MMP-3 produced by human intervertebral disc may be involved in the intervertebral disc degeneration, particularly in the initiation of matrix degradation of intervertebral disc.Journal of Spinal Disorders 12/1997; 10(6):493-8. · 1.21 Impact Factor
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ABSTRACT: The ultrastructure of ligamenta flava (LF) and interspinous ligaments (ISL) obtained from four patients who underwent surgery for vertebral fracture (control group) and five patients operated for disc herniation was studied. The fine structure of LF was composed of elastic and elaunin fibers. Small diameter collagen fibrils were found between the elastic system fibers. The ISL was constituted predominantly of collagen fibrils. Elastic fibers were seen in the most ventral part of the ligament. In ISL and LF of the control group, the cells were fibroblastic-like cells. Chondrocytes were present only near their attachment sites. The proteoglycans were demonstrated between the collagen fibrils, and they appeared to form a regular interfibrillar linking. In ligaments obtained from patients with disc herniation, several modifications were found. The fibroblasts transformed into chondrocytic cells, which were surrounded by a pericellular matrix rich in proteoglycan filaments. A few cells that had suffered necrosis were found. Alterations in the collagen-proteoglycans arrangement also were evidenced. The proteoglycan filaments were randomly oriented to the collagen fibrils.Spine 05/1990; 15(4):262-8. · 2.16 Impact Factor