Are fibroblasts involved in joint destruction?

• Published in: Annals of the rheumatic diseases 2005-11, Vol.64 (suppl 4), p.iv52-iv54
• Main Authors: Pap, T, Meinecke, I, Müller-Ladner, U, Gay, S
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Arthritis; Arthritis, Rheumatoid - enzymology; Arthritis, Rheumatoid - pathology; Biological and medical sciences; Cytokines; Diseases of the osteoarticular system; Enzymes; Extracellular matrix; Fibroblasts; Fibroblasts - enzymology; Fibroblasts - physiology; Genotype & phenotype; Humans; joint destruction; Ligands; Lymphocytes; matrix metalloproteinase; Matrix Metalloproteinases - biosynthesis; Medical sciences; Mice; Mice, SCID; MMP; MMPs; Prostheses; rheumatoid arthritis; SCID; severe combined immunodeficiency; Studies; synovial fibroblasts; Synovial Membrane - enzymology; Synovial Membrane - pathology; TIMP; tissue inhibitor of metalloproteinase; TNF; Tumor necrosis factor-TNF; tumour necrosis factor
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2005.042424

[...]it has been demonstrated that RA synovial fibroblasts release large amounts of the ligand for the receptor activator of nuclear factor β (RANKL), which mediates the differentiation of bone resorbing osteoclasts from their macrophage precursors. 2 Direct degradation of extracellular matrix by RA synovial fibroblasts is mediated through the attachment to cartilage and subsequent release of matrix degrading enzymes, particularly matrix metalloproteinases (MMPs) and cathepsins. 3 ACTIVATION OF RA SYNOVIAL FIBROBLASTS Although inflammatory cytokines such as tumour necrosis factor α (TNFα) have been demonstrated to stimulate RA synovial fibroblasts to produce such matrix degrading enzymes, the activation of these RA synovial fibroblasts is maintained even in the absence of continuous stimulation by proinflammatory factors. In line with this concept, we have shown that the overexpression of TIMP 1 and TIMP 3 by gene transfer may result in a marked reduction of the invasiveness of RA synovial fibroblasts. 22 Interestingly, TIMP 3 not only inhibits the degradation of extracellular matrix but shows a number of features that are distinct from other TIMPs. [...]TIMP 3 can prevent the shedding of cell membrane proteins such as the TNF receptor, 23 the interleukin (IL)-6 receptor, 24 and of TNFα-converting enzyme (TACE).