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

Abstract

OBJECTIVES—The active form of vitamin D₃, 1α,25 dihydroxyvitamin D₃ (1,25D₃), through its interaction with vitamin D receptors (VDR), is reported to effect a variety of anabolic and catabolic events, especially in bone and cartilage tissues. As cartilage degradation and tissue remodelling are characteristic features of the rheumatoid lesion, the distribution and expression of VDR at sites of cartilage erosion was examined.
METHODS—Immunolocalisation techniques using a rat monoclonal antibody to VDR and an alkaline phosphatase conjugated avidin/biotin detection system were used to examine VDR in 18 specimens of cartilage-pannus junction, 10 specimens of rheumatoid synovium or cartilage tissue, and four primary cultures of adherent rheumatoid synovial cells (RSC). For comparison, VDR expression was examined in 10 specimens of normal, healthy age matched articular cartilage.
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 chondrocytes 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 variability in both the numbers and proportions of macrophages or synovial fibroblasts 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 cartilage-pannus junction; was associated with various cell types, including chondrocytes, but not exclusively with CD68⁺ macrophages. The focal nature of VDR expression within the rheumatoid lesion suggests a contributory role for 1α,25D₃ in the pathophysiological processes of rheumatoid arthritis.

 Keywords: vitamin D receptor; vitamin D metabolites; rheumatoid arthritis

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Figure 1  .

Immunolocalisation of VDR in rheumatoid tissues, normal cartilage, and primary synovial cell cultures. (a) VDR production (red stain) by a proportion of synovial cells close to the CPJ. (b) VDR expression by cells at the cartilage interface (arrows) and by some chondrocytes at the CPJ. (c) Note absence of VDR expression by chondrocytes of normal articular cartilage. (d) Negative control: adjacent tissue section to (b) in which primary rat antibody was substituted with normal rat IgG. (e) VDR expression by cells of the synovial lining layer and a proportion of sub-lining synoviocytes. (f) VDR production by endothelial cells and a proportion of the rheumatoid synoviocytes. (g) VDR expression by chondrocytes close to the CPJ. (h) Primary culture of RSC stained for VDR with Fast Red (i) same field as (h) stained with macrophage marker, CD68 (green). (j) and (k) Negative controls for the staining procedures used in (h) and (i) respectively. Note that all the VDR staining is intracellular; and that all micrographs also illustrate negatively stained cells. (a) and (b) Bar = 35 µm, (c) and (d) bar = 50 µm, (e) and (f) bar = 25 µm, (g), (h), (i), (j) and (k) bar = 20 µm.