Observations on the microenvironmental nature of cartilage degradation in rheumatoid arthritis

Figure 1  .

Bidirectional erosion of articular cartilage and variations in cellular composition at sites of cartilage erosion. (A) Photomicrograph showing synovial pannus overlay of cartilage and bone. Note increased synthesis of proteoglycan by chondrocytes. Methylene blue, bar = 70 µm. (B) Bidirectional attack on articular cartilage with multinucleated osteoclasts/chondroclasts (arrows) on the subchondral side and PMNs and monocytes of the synovial tissue. Methylene blue, bar = 70 µm. (C) Bidirectional erosion of cartilage with a mixed population of cells and blood vessels at the subchondral interface, and a clearly defined synovial cell layer at the cartilage interface. Toluidine blue, bar = 70 µm. (D) Cartilage erosion site stained for α napthyl acetate esterase (αNA). Note strongly stained cells, especially in close association with cartilage matrix. Bar = 70 µm. (E) Focal accumulation of αNA positive cells at cartilage-pannus junction. Bar = 70 µm. (F) Cellular heterogeneity at cartilage erosion site. Note the variable morphologies of synovial cells and the lack of chondrolytic activity by the chondrocytes. Toluidine blue, bar = 50 µm.

Figure 2  .

Examples of microenvironmental proteinase expression at the rheumatoid lesion. (A) and (B) PMNs stained for chloroacetate esterase at the cartilage-pannus junction. Observations of PMNs were usually confined to thin overlays of synovial tissue, usually representing early erosive lesions. Bars = 30 µm. (C) and (D) Mast cells stained for tryptase with evidence of extracellular enzyme often associated with stromal oedema and matrix disruption (arrows). Bars = 70 µm and 30 µm respectively. (E) and (F) Extensive expression of acid phosphatase by cells at the cartilage-pannus junction (E), and by a proportion of larger macrophagic cells (F). Bars = 30 µm.

Figure 3  .

Heterogeneity of specific cell types at bone:pannus junctions and subchondral erosion sites. (A) Bone:pannus junction showing focal variations in cellularity and the expression of acid phosphatase activity. Bar = 70 µm. (B) High power magnification of (A) showing acid phosphatase positive cells in juxtaposition with mineralised bone. Bar = 30 µm. (C) Subchondral bone fragment showing alkaline phosphatase staining of osteoblastic cells interspersed with an osteoclast (arrow). Bar = 30 µm. (D) Alkaline phosphatase activity of osteoblasts in subchondral bone at site of extensive remodelling. Bar = 30 µm. (E) Osteoclasts stained for acid phosphatase at site of subchondral bone resorption. Bar = 30 µm. (F) Multinucleated chondroclasts stained for acid phosphatase at subchondral site. Note resorptive attachment to hyaline cartilage. Bar = 30 µm.

Figure 4  .

Examples of some unusual histological observations of the rheumatoid lesion. (A) Cartilage erosion site in which the chondrocytes demonstrate a `normal' morphology at the junction and the retention of this by the apparently displaced chondrocytes (arrow). Methylene blue, bar = 30 µm. (B) Cartilage-pannus junction characterised by focal accumulations of mast cells (arrows) at the cartilage interface. Note the pronounced chondrolytic activity of subjacent chondrocytes (compared with (A)). Methylene blue, bar = 40 µm. (C) and (D) Unusual accumulations of acid phosphatase positive cells within hyaline cartilage. Evidence of blood vessels and blood cells (arrows) suggests a subchondral infiltration with mono and binucleated cells strongly positive for acid phosphatase—possibly immature multinucleated cells. Bars = 70 µm and 30 µm, respectively. (E) Cartilage-pannus junction with multinucleated giant cells stained for acid phosphatase in contact with hyaline cartilage. Bar = 30 µm. (F) Cartilage-pannus junction showing a group of small blood vessels at the forefront of the invasive pannus tissue. Methylene blue, bar = 30 µm.

Figure 5  .

Esterase and acid phosphatase production by giant cells of rheumatoid synovium. α Napthyl esterase staining of giant cells in the synovial lining (A) and intimal (B) layers. Acid phosphatase staining of giant cells in the synovial lining (C) and intimal (D) layers. Bars = 30 µm all micrographs.

Figure 6  .

Microenvironmental observations related to sites of cartilage erosion. (a) Cartilage collagen loss at the rheumatoid lesion. Note abundant collagenous matrix (red) of the overlying pannus tissue. Van Giesons, bar = 70 µm. (b) Extracellular mast cell tryptase (red) indicative of mast cell degranulation at cartilage erosion site, together with cartilage bound stromelysin 1 (brown). Dual immunostaining, ⁴ bar = 30 µm. (c) Intra and extracellular non-specific esterase (brown) produced by cells at the cartilage-pannus interface. Note the relative absence of enzyme from pannus cells remote from the junction. α Napthyl acetate esterase. ⁶ Bar = 30 µm. (d) Focal production of interleukin 1β (brown) by a group of cells adjacent to area of extracellular mast cells tryptase (red, arrow). Dual immunostaining.⁴ Bar = 30 µm. (e) Stromelysin 1 distribution at cartilage-pannus junction. Note patchy distribution with relatively little enzyme in supporting pannus tissue. FITC immunostaining. ⁴ Bar = 30 µm. (f) Collagenase 1 distribution at cartilage-pannus junction restricted to the cartilage surface and showing diffusion within the matrix. Note relative absence of enzyme in overlying pannus tissue. FITC immunostaining. ¹ Bar = 30 µm.

Figure 7  .

Schematic illustration of potential cellular interactions and cyclical events that may contribute to chronic inflammation and cartilage erosion at the cartilage:pannus junction. Cartilage represented by shaded area. RF, rheumatoid factors; PA, plasminogen activator.