The proteins of homeobox (HOX) genes are transcription regulators involved in cell type-specific differentiation and patterning of the body plan in vertebrates. Particularly, the HOXD family is involved in limb formation in mice and chicks. There is also some evidence that the HOXD9 gene, a member of the HOXD family, is involved in the pathology of rheumatoid arthritis (RA). The purpose of the present study was to determine if the HOXD9 protein was expressed in RA synovium and then to characterize the HOXD9-expressing cell. Western blotting and immunohistochemical analysis showed that the HOXD9 protein was expressed in the synovium from patients with RA, but not in those from patients with osteoarthritis or healthy individuals. The HOXD9-positive cells were localized in both the lining and sublining areas of the synovium. Furthermore, fluorescent double-staining showed that the HOXD9 protein was expressed in fibroblast-like synoviocytes (FLS). These findings not only indicate that the HOXD9 gene is exclusively expressed in the RA synovium but also suggest that the HOXD9 gene contributes to the pathology of rheumatoid arthritis through the FLS.

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