Vitamin D receptors in the rheumatoid lesion: expression by chondrocytes, macrophages, and synoviocytes

Objectives-The active form of vitamin D-3, 1 alpha,25 dihydroxyvitamin D-3 (1,25D(3)), through its interaction with vitamin D receptors (VDR), is repo rted to effect a variety of anabolic and catabolic events, especially in bo ne and cartilage tissues. As cartilage degradation and tissue remodelling a re characteristic features of the rheumatoid lesion, the distribution and e xpression of VDR at sires of cartilage erosion was examined. Methods-Immunolocalisation techniques using a rat monoclonal antibody to VD R and an alkaline phosphatase conjugated avidin/biotin detection system wer e used to examine VDR in 18 specimens of cartilage-pannus junction, 10 spec imens of rheumatoid synovium or cartilage tissue, and four primary cultures of adherent rheumatoid synovial cells (RSC). For comparison, VDR expressio n was examined in 10 specimens of normal, healthy age matched articular car tilage. Results-VDR was demonstrated in 15 of 18 cartilage-pannus junctions either at the interface (8 of 18), within the pannus tissue (12 of 18), and by cho ndrocytes often close to the erosive lesion (10 of 18). All the rheumatoid synovial tissue and 5 of 10 cartilage specimens showed cells with positive staining, but the extent of this was variable. Negligible VDR staining was observed for normal cartilage. Primary cultures of RSC also showed variabil ity in both the numbers and proportions of macrophages or synovial fibrobla sts stained for VDR (range 10-50%), this being more common in cultures with a high proportion of macrophages. Conclusions-VDR expression has been demonstrated by most specimens of carti lage-pannus junction; was associated with various cell types, including cho ndrocytes, but not exclusively with CD68(+) macrophages. The focal nature o f VDR expression within the rheumatoid lesion suggests a contributory role for 1 alpha,25D(3) in the pathophysiological processes of rheumatoid arthri tis.