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.