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: Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in the elderly, and ligamentum flavum (LF) hypertrophy is an important cause of LSCS. Matrix metalloproteinase 13 (MMP13) can degrade fibrillar collagens and elastic microfibrils, and is involved in inflammation and fibrosis. The purpose of this study was to compare the expression of MMP13 in the LF from LSCS patients with diabetes mellitus [DM (+)] with that in the LF from patients without DM [DM (-)] and to analyze the relationship among DM, MMP13 expression, and LF hypertrophy. LFs from 11 DM (+) and 24 DM (-) LSCS patients were analyzed in this study. Histology analysis using hematoxylin and eosin and Masson's trichrome stain was performed for each LF. The expression of MMP13 was analyzed by quantitative real-time PCR. The thickness of LF was measured by CT. In the LF from DM (+) LSCS patients, the elastic fibers were more disorganized and had lower volumes than in the LF from DM (-) LSCS patients, while more fibrotic tissue was observed in the LF from DM (+) than from DM (-) LSCS patients. MMP13 expression was significantly higher in the LF from DM (+) LSCS patients (0.46 ± 0.61 vs. 0.05 ± 0.09, P = 0.002). The LF from the DM (+) LSCS patients was significantly thicker than that from the DM (-) LSCS patients (5.0 ± 0.9 vs. 3.1 ± 0.8 mm, P < 0.01), and the thickness was correlated with the expression of MMP13 (correlation coefficient = 0.43, P = 0.01, Pearson's correlation test). DM-related MMP13 expression can be one of the factors contributing to fibrosis and hypertrophy of the LF. Further research on the mechanism of this process may lead to new therapies for LF hypertrophy.Journal of Orthopaedic Science 08/2011; 16(6):785-90. · 0.96 Impact Factor
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ABSTRACT: Spinal stenosis and degenerative spondylolisthesis share many symptoms and the same treatment, but their causes remain unclear. Bone mineral density has been suggested to play a role. The aim of this study was to investigate differences in spinal bone density between spinal stenosis and degenerative spondylolisthesis patients. 81 patients older than 60 years, who underwent DXA-scanning of their lumbar spine one year after a lumbar spinal fusion procedure, were included. Radiographs were assessed for disc height, vertebral wedging, and osteophytosis. Pain was assessed using the Low Back Pain Rating Scale pain index. T-score of the lumbar spine was significantly lower among degenerative spondylolisthesis patients compared with spinal stenosis patients (-1.52 versus -0.52, P = 0.04). Thirty-nine percent of degenerative spondylolisthesis patients were classified as osteoporotic and further 30% osteopenic compared to only 9% of spinal stenosis patients being osteoporotic and 30% osteopenic (P = 0.01). Pain levels tended to increase with poorer bone status (P = 0.06). Patients treated surgically for symptomatic degenerative spondylolisthesis have much lower bone mass than patients of similar age treated surgically for spinal stenosis. Low BMD might play a role in the development of the degenerative spondylolisthesis, further studies are needed to clarify this.BioMed research international. 01/2013; 2013:123847.
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ABSTRACT: Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in chronic inflammatory disease, but its role in spinal diseases is unknown. The purpose of this study is to investigate the role of CX3CL1/CX3CR1 chemokine on hypertrophy of the ligamentum flavum (LF) in degenerative lumbar stenosis (DLS) compared with that of non-degenerative spinal condition (NDS) of the lumbar spine and correlation between expression of CX3CL1/CX3CR1 chemokine and thickness of LF. The mRNA concentrations of CX3CL1/CX3CR1 chemokine were analyzed in the surgically obtained LF specimens from DLS (n = 10) and NDS (n = 11) by real-time PCR. The localization of CX3CL1/CX3CR1 chemokine within the LF was determined using immunohistochemical study. Plasma levels of soluble FKN (sFKN) were measured by enzyme-linked immunosorbent assay, respectively. The thickness of the LF was measured with axial T1-weighted MRI. The cells that express CX3CL1/CX3CR1 chemokine ratio in the LF observed in DLS group were substantially higher than in NDS group. In ELISA, the plasma levels of sFKN was significantly increased in DLS compared with patients in the other groups (p = 0.006). There was greater CX3CL1/CX3CR1 expression in DLS as quantified by RT-PCR (p = 0.004, 0.010). Thickness of LF in patients was significantly correlated with serum CX3CL1 level (R2 = 0.824, p = 0.003) and with mRNA expression of CX3CL1/CX3CR1 (R2 = 0.671, p = 0.000) (R2 = 0.514, p = 0.001). This study identified for the first time that increases in CX3CL1 and CX3CR1-expressing cells are significantly related to LF hypertrophy.Connective tissue research 09/2013; · 1.55 Impact Factor