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Expression
of Matrix Metalloproteinase 7 (Matrilysin) in Human Osteoarthritic Cartilage
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Satoru Ohta,
Kazushi Imai, Kaname Yamashita, Tadami Matsumoto, Isao Azumano, and Yasunori
Okada |
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Department
of Molecular Immunology and Pathology (SO, KI, KY, YO), Cancer Research
Institute, Kanazawa University, and Department of Orthopedic Surgery (SO,
TM), School of Medicine, Kanazawa University, Kanazawa; and Fuji Chemical
Industries, Ltd. (IA), Takaoka, Japan |
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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-1[alpha]
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. |
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