Bone destruction in arthritis.

نویسنده

  • E M Gravallese
چکیده

Rheumatoid arthritis (RA) is characterised by the presence of an inflammatory synovitis accompanied by destruction of joint cartilage and bone. Destruction of cartilage matrix results predominantly from the action of connective tissue proteinases released by RA synovial tissues, chondrocytes, and pannus tissue. Several lines of evidence in RA and in animal models of arthritis support a role for osteoclasts in the pathogenesis of bone erosions. RA synovial tissues produce a variety of cytokines and growth factors that may increase osteoclast formation, activity, and/or survival. These include interleukin 1alpha (IL1alpha) and beta, tumour necrosis factor alpha (TNFalpha), IL11, IL17, and macrophage colony stimulating factor (M-CSF). Receptor activator of NFkappaB ligand (RANKL) is an essential factor for osteoclast differentiation and also functions to augment T cell-dendritic cell cooperative interactions. CD4+ T cells and synovial fibroblasts derived from RA synovium are sources of RANKL. Furthermore, in collagen induced arthritis (CIA), blockade with osteoprotegerin (OPG), a decoy receptor for RANKL, results in protection from bone destruction. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, arthritis was generated in the RANKL knockout mouse using a serum transfer model. Despite ongoing inflammation, the degree of bone erosion in arthritic RANKL knockout mice, as assessed by microcomputed tomography and correlated histopathological analysis, was dramatically reduced compared with that seen in arthritic control mice. Cartilage damage was present in both the arthritic RANKL knockout mice and in arthritic control littermates, with a trend toward milder cartilage damage in the RANKL knockout mice. This study supports the hypothesis that osteoclasts play an important part in the pathogenesis of focal bone erosion in arthritis, and reveals distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis. Future directions for research in this area include the further investigation of a possible direct role for the RANKL/RANK/OPG system in cartilage metabolism, and the possible role of other cell types and cytokines in bone erosion in arthritis.

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عنوان ژورنال:
  • Annals of the rheumatic diseases

دوره 61 Suppl 2  شماره 

صفحات  -

تاریخ انتشار 2002