Figure 4.
Effect of PS-341 on PG/PS-induced alterations in the histologic appearance of the joint, 4 weeks after the induction of arthritis. (A) Normal saline control. Typical appearance of the articular cartilage (c), the subchondral bone (b), and the synovial villus and membrane (s). (B) Arthritic joint (vehicle-treated, PG/PS). Dramatic expansion and development of the synovial membrane and synovial villi into the erosive pannus (p), which is associated with the degradation of the articular cartilage (c) and subchondral bone (b). Inflammatory cell infiltration (arrows) is evident in the pannus and in the medullary canals (m) of the subchondral bone. Cellular infiltrate and fibrin (i) is seen in the articular space. (C) PS-341- (0.3 mg/kg/day) treated, PG/PS-induced arthritis. The pannus (p) remains present with the synovial membrane(s) thickened but exhibits a marked reduction in the number of inflammatory cells. Degradation of the articular cartilage (c) is attenuated and confined to the cartilage surface (arrow). Little or no erosion of the subchondral bone (b) is apparent, and there is minimal erosive activity and inflammatory cell infiltration in the medullary canals (m) of the subchondral bone. (Magnification, ×20; scale bar, 50 μm).