Experimental Arthritis Models in the Study of the Mechanisms of Articular Cartilage Loss in Rheumatoid Arthritis

Role of TNF alpha in the induction of antigen induced arthritis in the rabbit and the anti-arthritic effect of species specific TNF alpha neutralising monoclonal antibodies.

“…As zo/Macro with the effect on joint swelling, increasing the concentration of neutralising antibody fivefold (457) gave no further reduction in leucocyte infiltration into the joint fluid. As determined ared with by FACS analysis, antibody R6 caused a significant reduction in the expression of the [32 integrin subunits CD1 lb and CD18 on lymphocyte sized cells in the synovial cavity, but did not significantly reduce their expression on monocyte/macrophage sized cells in the arthritic joints (table 2). The concentrations of PGE2 in fluids from the arthritic joints were more than twice those of the controls.…”

Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs

“…Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease of unknown etiology characterized by chronic synovitis with subsequent articular bone and cartilage destruction (1,2). Chronic inflammation with hyperplasia of synovial lining cells, including synovial fibroblasts, are the histological characteristics of RA.…”

2nd International meeting on synovium cell biology, physiology and pathology. Canterbury, United Kingdom, 21-23 September 1994. Proceedings and abstracts.

“…26 In a recent study, Qu et al further addressed this question by examining synovial membrane samples for three markers of cell proliferation: proliferating cell nuclear antigen, C-myc proto-oncogene, and nucleolar organiser regions.26 All three markers indicated that there was active proliferation in the synovial lining of RA patients. Double labelling experiments indicated that the proliferating cells were fibroblastic in type, as they were type I procollagen positive and CD68 negative.…”

“…However, these animals showed no inhibition of cartilage proteoglycan loss.25 This substantiates the growing belief that tissue damage and inflammation in the rheumatoid joint may not be causally linked. 26 Two additional problems are faced by antibodies. First, if articular cartilage chondrocytes are producing the cytokines which, acting in an autocrine fashion, stimulate the degradation of cartilage, then neutralising antibodies may not be able to penetrate the cartilage to switch off synthesis.…”

“…25 This mechanism, however, appears to be counteracted by overexpression on RA synovial fluid cells of the Apo-1/Fas antigen, which can promote programmed cell death. 26 On the basis of the above findings it is possible that disruption of the delicate balance between cell proliferation, however low, and cell death contributes to synovial hyperplasia.…”