Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5

S YoshidaDepartments of Pathology, School of Medicine, Kurume University, Japan;Departments of Orthopaedic Surgery, School of Medicine, Kurume University, Japan

F ArakawaDepartments of Pathology, School of Medicine, Kurume University, JapanCorrespondence[email protected]

F HiguchiDepartment of Orthopaedic Surgery, Kurume University Medical Centre, Japan

Y IshibashiDepartment of Orthopaedic Surgery, Kurume University Medical Centre, Japan

M GotoDepartment of Orthopaedic Surgery, Kurume University Medical Centre, Japan

Y SugitaDepartments of Pathology, School of Medicine, Kurume University, Japan

Y NomuraDepartments of Pathology, School of Medicine, Kurume University, Japan

D NiinoDepartments of Pathology, School of Medicine, Kurume University, Japan

K ShimizuDepartments of Pathology, School of Medicine, Kurume University, Japan

R AokiDepartments of Pathology, School of Medicine, Kurume University, Japan

K HashikawaDepartments of Pathology, School of Medicine, Kurume University, Japan

Y KimuraDepartments of Pathology, School of Medicine, Kurume University, Japan

K YasudaCell Innovator Inc., Venture Business Laboratory of Kyushu University, Japan

K TashiroLaboratory of Molecular Gene Technology, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Japan

S KuharaLaboratory of Molecular Gene Technology, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Japan

K NagataDepartments of Orthopaedic Surgery, School of Medicine, Kurume University, Japan

K OhshimaDepartments of Pathology, School of Medicine, Kurume University, Japan

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Abstract

Objectives: The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells, an important source of cytokines and chemokines, which are associated with inflammation. The aim of this study was to evaluate gene expression in the microdissected synovial lining cells of RA patients, using those of osteoarthritis (OA) patients as the control.

Methods: Samples were obtained during total joint replacement from 11 RA and five OA patients. Total RNA from the synovial lining cells was derived from selected specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis. In addition, the expression of significant genes was confirmed immunohistochemically.

Results: The 14 519 genes detected by cDNA microarray were used to compare gene expression levels in synovial lining cells from RA with those from OA patients. Cluster analysis indicated that RA cells, including low- and high-expression subgroups, and OA cells were stored in two main clusters. The molecular activity of RA was statistically consistent with its clinical and histological activity. Expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the synovium of RA than in that of OA. Immunohistochemically, the lining synovium of RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was seen in microarray analysis combined with LMD.

Conclusions: Our findings indicate an important role for lining synovial cells in the inflammatory and proliferative processes of RA. Further understanding of the local signalling in structural components is important in rheumatology.

Acknowledgements

We thank Konomi Takasu for her excellent technical support.

Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5

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Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5

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