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Expression of Granzyme B in Human Articular Chondrocytes
KIWAMU HORIUCHI, SEIJI SAITO, RYOHEI SASAKI, TAISUKE TOMATSU, and YOSHIAKI TOYAMA
ABSTRACT.
Methods. Normal cartilage samples were obtained from 9 resected joints and RA cartilage samples were obtained from 12 patients with RA during joint replacement surgery. Cartilage sections were analyzed by immunohistochemistry for the presence of GrB, and the mRNA expression of GrB in chondrocytes was analyzed by in situ hybridization and nonquantitative and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of perforin (PFN) was also assessed. Apoptotic chondrocytes were detected using TUNEL staining and their morphology was examined using electron microscopy. Results. The immunohistochemical analyses revealed GrB and PFN expression in normal chondrocytes and a larger number of GrB and PFN-positive chondrocytes in RA cartilage. In situ hybridization and RT-PCR confirmed the expression of GrB and PFN mRNA, and semiquantitative RT-PCR showed elevated concentrations of GrB and PFN expression in RA chondrocytes. The distribution of GrB and PFN-positive cells in the RA cartilage samples was similar to that of apoptotic cells. Conclusion. GrB and PFN expression is present in normal human articular chondrocytes and elevated in RA chondrocytes. The targets and precise functions of GrB expressed in chondrocytes remain to be determined, but GrB may be involved in the remodeling mechanism of matrix macromolecules and the endogenous degradation of RA cartilage. (J Rheumatol 2003;30:1799-810) Key Indexing Terms:
GRANZYME B
From the Institute of Rheumatology, Tokyo Women's Medical University, Tokyo; Division of Radiology, Kobe University Graduate School of Medicine, Kobe; and Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan. K. Horiuchi, MD; S. Saito, MD, PhD, Assistant Professor, Institute of Rheumatology, Tokyo Women's Medical University; R. Sasaki, MD, PhD, Division of Radiology, Kobe University Graduate School of Medicine; T. Tomatsu, MD, PhD, Professor, Institute of Rheumatology, Tokyo Women's Medical University; Y. Toyama, MD, PhD, Professor, Department of Orthopaedic Surgery, School of Medicine, Keio University. Address reprint requests to Dr. K. Horiuchi, Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054 Japan. E-mail: k-hori@muf.biglobe.ne.jp Submitted July 5, 2002; revision accepted January 30, 2003. |