Synovial fibroblasts spread rheumatoid arthritis to unaffected joints

Lefèvre1 S et al., Nature Medicine 15:1414-22 (2009)

Speaker: Wang Yu-Ren (王昱仁)                                          Time: 13:10-14:00, Jun. 2, 2010

Commentator: Dr. Wang Chrong-Reen (王崇任 醫師)       Place: Room 601

Abstract:

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease. About 1% of the world's population is afflicted bythis disease, women three times more often than men. Although the pathogenesis of RA remains largely unknown, recent studies suggest that RA synovial fibroblasts (RASFs) may play a key pathogenetic role. RA usually originates from few joints but subsequently attacks multiple joints. The aim of this study was to demonstrate that this phenomenon was mediated by transmigration of activated RASF.

The SCID mouse migration model was used. Primary implants containing RASFs were implanted with RASF-free contralateral implants in a variety of experimental settings. Histological sections of implants are evaluated to determine the fibroblast invasion and cartilage degradation. Immunohistochemistry was performed to detect the origin of invading cells. RASFs were injected 14 days after the implantation and internal organs of mice were analyzed to elucidate the route their migration. Transepithelial electrical resistance assay was used to measure the transmigratory potential of RASFs.

RASFs were able to invade and degrade primary implanted cartilages and contralaterally implanted ones. The invading cells were demonstrated to be of human origin. Vascularization but not wounding or ongoing wound healing might facilitate the invasion of RASFs from the primary implants into the contralateral ones. Injection of RASFs by different routes (subcutaneous, intraperitoneal and intravenous) led to destruction of implanted cartilages. Migration of RASF toward the cartilage was through the bloodstream, and the spleen was the only internal organ where RASFs could be detected. The transmigratory potentials of RASFs were increased as comparing with other cell lines such as osteoarthritis synovial fibroblasts.

Taken together, these data support the hypothesis that the destructive arthritis spreading between RA joints could be mediated by the transmigration of activated RASF.

References:

1.          Huber LC, et al. Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology 45: 669-75 (2006).

2.          Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 423:356-361(2003)

3.          Müller-Ladner U et al. Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am J Pathol 149:1607-1615(1996)