Cells of the synovium in rheumatoid arthritis. Chondrocytes

Abstract

Rheumatoid arthritis (RA) is one of the inflammatory joint diseases in a heterogeneous group of disorders that share features of destruction of the extracellular matrices of articular cartilage and bone. The underlying disturbance in immune regulation that is responsible for the localized joint pathology results in the release of inflammatory mediators in the synovial fluid and synovium that directly and indirectly influence cartilage homeostasis. Analysis of the breakdown products of the matrix components of joint cartilage in body fluids and quantitative imaging techniques have been used to assess the effects of the inflammatory joint disease on the local remodeling of joint structures. The role of the chondrocyte itself in cartilage destruction in the human rheumatoid joint has been difficult to address but has been inferred from studies in vitro and in animal models. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the disruption of the integrity of the cartilage matrix in RA.

Figure 1

Cytokine networks and cellular interactions in cartilage destruction in rheumatoid arthritis. This scheme represents the progressive destruction of the cartilage associated with the invading synovial pannus in rheumatoid arthritis. As a result of immune cell interactions involving T and B lymphocytes, monocyte/macrophages, and dendritic cells, several different cytokines are produced in the inflamed synovium as a result of the influx of inflammatory cells from the circulation and synovial cell hyperplasia. The upregulation of proinflammatory cytokines produced primarily in the synovium, but also by chondrocytes, results in the upregulation of cartilage-degrading enzymes, of the matrix metalloproteinase (MMP) and ADAM with thrombospondin-1 domains (ADAMTS) families, at the cartilage–pannus junction. Chemokines, nitric oxide (NO), and prostaglandins (PGs) also contribute to the inflammation and tissue catabolism. SDF, stromal cell-derived factor 1; TNF, tumor necrosis factor; TGF, transforming growth factor; IFN, interferon; Treg, regulatory T lymphocytes; Th, T helper cells.