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 [ρ] = 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-1α and/or tumor necrosis factor-α. 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.
|Number of pages||9|
|Publication status||Published - 1998 Jan|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Molecular Biology
- Cell Biology