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Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2000 Jan; Vol. 105 (2), pp. 143-50. - Publication Year :
- 2000
-
Abstract
- Herniated disc (HD), one of the major causes of low back pain, is often resolved spontaneously without surgical intervention. Resorption is associated with a marked increase in infiltrating macrophages, and the matrix metalloproteinases (MMP) MMP-3 and MMP-7 have been implicated in this phenomenon. We developed a murine organ culture model in which intact intervertebral discs were cocultured with peritoneal macrophages to investigate the role of MMPs in HD resorption. Using macrophages isolated from MMP-null mice, we report that macrophage-produced MMP-7 was required for proteoglycan degradation, loss of wet weight, and macrophage infiltration of cocultured discs. The inability of MMP-7-deficient macrophages to infiltrate discs could not be attributed to a defect in macrophage migration. MMP-7 was required for the release of the cytokine TNF-alpha from peritoneal macrophages. The generation of soluble TNF-alpha was essential for the induction of MMP-3 in disc cocultures, which in turn is required for the generation of a macrophage chemoattractant and subsequent macrophage infiltration. TNF-alpha release from macrophages was necessary but insufficient for disc resorption, which required macrophage infiltration. We conclude that there is extensive communication between macrophages and chondrocytes in HD resorption and that an essential component of this communication is the requirement for MMPs to release soluble bioactive factors.
- Subjects :
- Animals
Bone Resorption enzymology
Cell Migration Inhibition
Cells, Cultured
Coculture Techniques
Diffusion Chambers, Culture
Disease Models, Animal
Enzyme Induction
Intervertebral Disc cytology
Intervertebral Disc enzymology
Intervertebral Disc Displacement genetics
Intervertebral Disc Displacement pathology
Macrophages, Peritoneal cytology
Macrophages, Peritoneal drug effects
Macrophages, Peritoneal enzymology
Matrix Metalloproteinase 3 biosynthesis
Mice
Mice, Inbred Strains
Mice, Knockout
Intervertebral Disc Displacement enzymology
Matrix Metalloproteinase 7 metabolism
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 105
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 10642592
- Full Text :
- https://doi.org/10.1172/JCI7091