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Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage
1Department of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University, Japan.
Abstract:
Matrix metalloproteinases (MMP) consisting of at least 16 different molecules are thought to be involved in the degradation of extracellular matrix (ECM) macromolecules under various pathologic conditions. Among them, MMP-7 (matrilysin) is unique in that it has high specific activity against various ECM components such as cartilage proteoglycan. In the present study, we examined the expression and tissue localization of MMP-7 in articular cartilages of human osteoarthritis (OA). Immunohistochemistry using a monoclonal antibody specific to MMP-7 demonstrated that the proteinase is localized to the OA chondrocytes mainly in the superficial and transitional zones in 92% of the OA cases examined (36 of 39 cases). On average, approximately 30% of the total chondrocytes (29.1%+/-30.2%) were immunostained in the positive OA cartilage samples. In contrast, MMP-7 staining was found in 8% of the normal cartilage cases (1 of 12 cases), and only a few chondrocytes (0.15%+/-0.67%) in the superficial zone were immunostained. There was a linear correlation between degree (%) of the immunostained chondrocytes and Mankin scores (rho [rho] = 0.84). Immunoblot analysis of the culture media from the cartilage explants demonstrated MMP-7 in 65% of the OA cases (15 of 23 cases) and 8% of the normal specimens (1 of 12 cases). Reverse transcription-PCR demonstrated the specific amplicon in 68% of the OA cartilage cases (17 of 25 cases), whereas only 18% of the control (2 of 11 cases) amplified the product. In situ hybridization revealed that the chondrocytes in OA cartilage express MMP-7 mRNA. MMP-7 gene expression in cultured OA chondrocytes was enhanced by the treatment with interleukin-1alpha and/or tumor necrosis factor-alpha. These data demonstrate for the first time that MMP-7 is overexpressed in human OA cartilage and suggest that cytokine-induced MMP-7 may play an important role in the degradation of ECM macromolecules in the OA cartilage.
Insights
Matrix metalloproteinase-7 (MMP-7) is overexpressed in human osteoarthritis (OA) cartilage, particularly in chondrocytes. This suggests MMP-7 plays a key role in the extracellular matrix degradation characteristic of OA.
Area of Science:
- Biochemistry
- Molecular Biology
- Rheumatology
Background:
- Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix (ECM) degradation.
- MMP-7 (matrilysin) exhibits high activity against ECM components like cartilage proteoglycan.
- Osteoarthritis (OA) is characterized by ECM degradation in articular cartilage.
Purpose of the Study:
- To investigate the expression and localization of MMP-7 in human OA articular cartilage.
- To determine the correlation between MMP-7 expression and OA severity.
- To explore the regulation of MMP-7 gene expression in OA chondrocytes.
Main Methods:
- Immunohistochemistry using a monoclonal antibody specific to MMP-7.
- Immunoblot analysis of cartilage explant culture media.
- Reverse transcription-polymerase chain reaction (RT-PCR) for MMP-7 mRNA.
- In situ hybridization to localize MMP-7 mRNA expression.
- Treatment of cultured OA chondrocytes with cytokines (IL-1α, TNF-α).
Main Results:
- MMP-7 was localized to OA chondrocytes in 92% of examined OA cases, with approximately 30% of total chondrocytes stained.
- MMP-7 staining was significantly higher in OA cartilage (92%) compared to normal cartilage (8%).
- A linear correlation was observed between the percentage of MMP-7 positive chondrocytes and Mankin scores (OA severity).
- MMP-7 protein and mRNA were detected more frequently in OA cartilage than in normal cartilage.
- Interleukin-1α and tumor necrosis factor-α enhanced MMP-7 gene expression in cultured OA chondrocytes.
Conclusions:
- MMP-7 is significantly overexpressed in human OA articular cartilage.
- MMP-7 expression in chondrocytes correlates with OA severity.
- Cytokine-induced MMP-7 likely contributes to ECM degradation in OA cartilage.
- MMP-7 represents a potential therapeutic target for osteoarthritis.
