Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage

Satoru Ohta, Kazushi Imai, Kaname Yamashita, Tadami Matsumoto, Isao Azumano, Yasunori Okada

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73 Citations (Scopus)

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 [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.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalLaboratory Investigation
Volume78
Issue number1
Publication statusPublished - 1998 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Ohta, S., Imai, K., Yamashita, K., Matsumoto, T., Azumano, I., & Okada, Y. (1998). Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage. Laboratory Investigation, 78(1), 79-87.