Abstract
BackgroundRheumatoid arthritis synovial fibroblasts (RASFs) are known to travel via the bloodstream from sites of cartilage destruction to new locations where they reinitiate the destructive processes at distant articular cartilage surfaces. In this study, we examined the role of interleukin (IL)-1-induced cartilage changes and their chemotactic effect on RASF transmigratory capacity.MethodsTo investigate synovial fibroblast (SF) transmigration through endothelial layers, we used a modified Boyden chamber with an endothelioma cell layer (bEnd.5) as a barrier and IL-1-treated murine cartilage explants as a chemotactic stimulus for SFs from human tumor necrosis factor–transgenic (hTNFtg) mice. We injected recombinant IL-1 or collagenase into knee joints of wild-type mice, followed by tail vein injection of fluorescence-labeled hTNFtg SFs. The distribution and intensity of transmigrating hTNFtg SFs were measured by fluorescence reflectance imaging with X-ray coregistration. Toluidine blue staining was performed to evaluate the amount of cartilage destruction.ResultsHistomorphometric analyses and in vivo imaging revealed a high degree of cartilage proteoglycan loss after intra-articular IL-1 and collagenase injection, accompanied by an enhanced in vivo extravasation of hTNFtg SFs into the respective knee joints, suggesting that structural cartilage damage contributes significantly to the attraction of hTNFtg SFs into these joints. In vitro results showed that degraded cartilage was directly responsible for the enhanced transmigratory capacity because stimulation with IL-1-treated cartilage, but not with IL-1 or cartilage alone, was required to increase hTNFtg SF migration.ConclusionsThe present data indicate that structural cartilage damage facilitates the migration of arthritic SF into affected joints. The prevention of early inflammatory cartilage damage may therefore help prevent the progression of rheumatoid arthritis and its spread to previously unaffected joints.
Highlights
Rheumatoid arthritis synovial fibroblasts (RASFs) are known to travel via the bloodstream from sites of cartilage destruction to new locations where they reinitiate the destructive processes at distant articular cartilage surfaces
Numerous data have shown that IL-1, another key cytokine in RA, mediates cartilage and bone degradation in RA [13, 16, 32]. In line with these data, we found that IL-1-induced proteoglycan depletion in cartilage hip caps as well as in knee joints of WT mice resulted in an increased transmigration of human tumor necrosis factor–transgenic (hTNFtg) SFs in vitro and in vivo
Currently, not much is known about pathological changes that initiate and drive the progression of RA in very early stages of the disease, despite a consensus that there are molecular and cellular alterations, including changes in cartilage structure, that precede the onset of synovitis in RA [33,34,35,36,37,38]
Summary
Rheumatoid arthritis synovial fibroblasts (RASFs) are known to travel via the bloodstream from sites of cartilage destruction to new locations where they reinitiate the destructive processes at distant articular cartilage surfaces. Research in recent years has identified synovial fibroblasts (SFs) in the lining layer of the hyperplastic synovial membrane as key player in the Hillen et al Arthritis Research & Therapy (2017) 19:40 pannus They have been suggested to contribute to the spreading of disease by their ability to leave cartilage destruction sites, migrate via the bloodstream, and reinitiate the destructive process at distant articular cartilage surfaces [10]. Because the ability of RASFs to enter and leave the bloodstream was demonstrated in a SCID mouse coimplantation model, it must be at least in part independent on a stimulated immune system This suggests that cytokines implicated in immune processes and other signals attract RASFs to cartilage surfaces and facilitate their transmigration at sites of extravasation. Several lines of evidence suggest that cartilage damage, and the loss of proteoglycans, precedes the attachment and activation of SFs at least in animal models of RA [13, 14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
