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Matrix metalloproteinases lead to disc degradation, aging
Expression of major matrix metalloproteinases increases sharply between ages 16 and 30.
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NANTES, France — Collagen-degrading enzymes called major matrix metalloproteinases may help initiate a long chain of molecular events that lead to intervertebral disc degeneration and low-back pain resulting from aging.
Findings from a study conducted by German and Swiss investigators confirmed that major matrix metalloproteinases (MMP) play a key role in the degradation of intervertebral discs, including causing granular changes and mucous degeneration within the disc. The investigation, presented during the 4th Meeting of the Spine Society of Europe (SSE), here, earned the team of five researchers the 2002 Centerpulse SSE Basic Science Award.
According to lead investigator Christoph Weiler, MD, of the Institute of Pathology at the University of Munich, “This is the first study to link expression of MMPs to histomorphological signs of disc degeneration. We could show that there is an association between MMP expression and age, providing clear evidence that the aging disc contains more MMP-producing cells.”
Researchers studied MMP-1, -2, -3 and -9 because these enzymes have been shown to degrade matrix components like collagen types I, II, III and minor collagen types (IV, V, etc.) within discs; they have also shown the ability to degrade some non-collagen components, such as proteoglycans. The investigators used immunohistochemistry for most of the study and confirmed results using in situ hybridization (biopsy material) and in situ zymography.
Scientists examined the phenomenon of MMPs degrading discs in tissue sections of 30 cross-sections of cadaveric lumbar intervertebral discs (group 1). Discs were from individuals aged 0 to 86 years. Tissues were sectioned for immunolocalization of MMPs. In group one, researchers sought a correlation between MMP expression and histomorphological alterations in different anatomic regions.
Researchers also studied 30 fresh lumbar tissue specimens obtained from surgical patients (group 2) for in situ hybridization analysis. For the first group, researchers performed immunohistochemical staining for MMP-1, -2, -3 and –9, as well as for CD 68, a marker for a lysosomal enzyme that indicates a cell’s phagocytic activity.
They conducted histomorphologic analysis and in situ hybridization for MMP-2 and -3 expression, while in situ zymography was performed to detect gelatinolytic activity. Researchers individually assessed and analyzed histological data for the nucleus pulposus and annulus fibrosis using a special grading system (Histo Degeneration Score), which takes into account four different parameters: cell density (chondrocyte proliferation), tears and clefts, mucoid degeneration and granular matrix changes.
When investigators analyzed histomorphologic alterations in the fetal and infantile age group (0 to 9 years), they saw almost no signs of degenerative lesions; however, slight chondrocyte proliferation and minimal granular changes were seen in the nucleus pulposus of the young adolescent disc specimen.
MMP expression and histologic signs of disc degeneration were not significant. “In the 16-to-30-year age group, we found significant discal alterations with the formation of clefts, tears, focal chondrocytes, proliferation, significant granular matrix degeneration and minor mucous degeneration,” Weiler said.
For your information:
- Weiler C, Nerlich AG, Zipperer J, et al. Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Presented at the 4th Annual Meeting of the Spine Society of Europe. Sept. 11-14, 2002. Nantes, France.