Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Pigmented Villonodular Synovitis Suggests Their Potential Role for Joint Destruction

MITSUTOSHI UCHIBORI, YOSHIHIRO NISHIDA, IZURU TABATA, HIDESHI SUGIURA, HIROATSU NAKASHIMA, YOSHIHISA YAMADA, and NAOKI ISHIGURO

ABSTRACT.

Objective. Pigmented villonodular synovitis (PVNS) is an uncommon idiopathic, proliferative synovial disease. Since matrix metalloproteinases (MMP) are assumed to play an important role in the pathogenesis of PVNS, we examined the expression and activity of MMP and tissue inhibitor of metalloproteinases (TIMP) in PVNS.

Methods. Synovial tissue samples were obtained from 10 patients with PVNS (knee 8, ankle 2) and 4 patients each with rheumatoid arthritis (RA) or osteoarthritis (OA) for comparison. Protein deposition and mRNA expression were determined by conventional immunohistochemical studies and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Gelatin zymography was performed for detection of gelatin-degrading activity. The quantity of MMP and TIMP was measured by ELISA.

Results. Intense immunostaining for MMP-1 was detected in both the multinucleated giant cells and mononuclear cells, whereas TIMP-1 was weakly positive. MMP-9 immunostained predominantly in the multinucleated cells, whereas other MMP and TIMP were weakly detected. RT-PCR analysis showed that mRNA expression of MMP-9 was stimulated in PVNS, whereas MMP-2 mRNA was not, compared to RA or OA. The gelatin zymogram indicated protease activities predominantly at 92 kDa and 67 kDa. In accord with the immunostaining results, the amount of MMP-1 and MMP-9 protein was significantly higher than that of TIMP-1 and MMP-2, respectively.

Conclusion. We characterized the expression and activity of MMP in PVNS and observed that PVNS tissues predominantly produce MMP-1 and MMP-9. Given that PVNS occasionally induces joint destruction, stimulated expression of MMP-1 and MMP-9 may contribute to the invasive activity and the bone and cartilage loss in PVNS. (J Rheumatol 2004;31:110-9)

Key Indexing Terms:

PIGMENTED VILLONODULAR SYNOVITIS
MATRIX METALLOPROTEINASES
TISSUE INHIBITOR OF METALLOPROTEINASE
JOINT DESTRUCTION
IMMUNOHISTOCHEMISTRY

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From the Department of Orthopaedic Surgery, Aichi Prefectural Hospital, Aichi; and Department of Orthopedic Surgery, Nagoya University School of Medicine, Aichi, Japan.

Supported in part by the Ministry of Education, Science and Culture of Japan (Grant-in-aid no. 13770790).

M. Uchibori, MD, Department of Orthopedic Surgery, Aichi Prefectural Hospital; Y. Nishida, MD, PhD, Senior Lecturer; I. Tabata, MD; H. Sugiura, MD, PhD, Assistant Professor; H. Nakashima, MD; Y. Yamada, MD; N. Ishiguro, MD, PhD, Professor, Department of Orthopedic Surgery, Nagoya University School of Medicine.

Address reprint requests to Dr. Y. Nishida, Department of Orthopedic Surgery, Nagoya University School of Medicine, 65 Tsurumai, Nagoya, Aichi 466-8550, Japan.

Submitted September 24, 2002; revision accepted June 24, 2003.

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