Are fibroblasts involved in joint destruction?
Are fibroblasts involved in joint destruction?
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DOI：
10.1136/ard.2005.042424
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发表时间：
2005-11-01
影响因子：
27.4
通讯作者：
Gay, S
中科院分区：
文献类型：
--
作者：
Pap, T;Meinecke, I;Gay, S
SYNOVIAL FIBROBLASTS IN RA Synovial fibroblasts in the most superficial lining layer of the hyperplastic RA synovium have been assigned an important role in the pathogenesis of RA and associated with key processes leading to the degradation of extracellular matrix. It has been understood that these cells exhibit an altered morphology and are characterised by changes in their behaviour that show certain similarities to tumours. Therefore, the phenotype of these cells has been termed ‘‘transformed appearing’’,‘‘tumour-like’’1 or—reflecting the clear differences with malignancies—‘‘activated’’. As part of a cellular network, RA synovial fibroblasts are involved in the destruction of extracellular matrix both by direct mechanisms and through interaction with neighbouring cells such as macrophages. Thus, it has been demonstrated that RA synovial fibroblasts release large amounts of the ligand for the receptor activator of nuclear factor b (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. 3ACTIVATION OF RA SYNOVIAL FIBROBLASTS Although inflammatory cytokines such as tumour necrosis factor a (TNFa) 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. This notion is derived from different in vitro studies as well as from data on the severe combined immunodeficient (SCID) mouse model of rheumatoid cartilage destruction. 4 Initially, this model was designed to investigate the fate of inflammatory cells, particularly lymphocytes in the inflamed RA synovium. However, by implanting rheumatoid synovial tissue into SCID mice, it was shown that lymphocyte infiltrates disappear with time, whereas lining layer synoviocytes survive. 5 6 Interestingly, these RA synovial fibroblasts not only survived in SCID mice recipients but also maintained their characteristic biological features. Based on these observation, the SCID mouse co-implantation model was developed as a new model for studying molecular mechanisms of rheumatoid joint destruction in vivo. 7 To imitate the situation in a rheumatoid joint, human RA synovium was implanted together with normal human cartilage under the renal capsule in SCID mice. It was shown that RA synovial tissue and normal human cartilage can be kept in SCID mice
