title: Structural cartilage damage attracts circulating rheumatoid arthritis synovial fibroblasts into affected joints.
abstract: 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. In this study, we examined the role of interleukin (IL)-1-induced cartilage changes and their chemotactic effect on RASF transmigratory capacity.
  
  
  
  To 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.
  
  
  
  Histomorphometric 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.
  
  
  
  The 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.
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, D3, 48149, Muenster, Germany.|Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hillen
authors.affiliation: Interdisciplinary Centre for Clinical Research, University Hospital Muenster, Muenster, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Geyer
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, D3, 48149, Muenster, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Heitzmann
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, D3, 48149, Muenster, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Beckmann
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, D3, 48149, Muenster, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Krause
authors.affiliation: Interdisciplinary Centre for Clinical Research, University Hospital Muenster, Muenster, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Winkler
authors.affiliation: Department of General Internal Medicine, Nephrology, Hypertension Diseases and Rheumatology, University Hospital Muenster, Muenster, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.affiliation: Interdisciplinary Centre for Clinical Research, University Hospital Muenster, Muenster, Germany.|Department of Radiology, St. Franziskus Hospital GmbH Muenster, Muenster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, D3, 48149, Muenster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, D3, 48149, Muenster, Germany. korba@uni-muenster.de.
authors.forename: Adelheid
authors.identifier: 0000-0002-0106-903X
authors.initials: A
authors.lastname: Korb-Pap
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002232:Carbocyanines / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007719:Knee Joint / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C574020:1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine; D002232:Carbocyanines; D005456:Fluorescent Dyes; D007375:Interleukin-1; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: In vivo imaging; Mouse model; Rheumatoid arthritis; Synovial fibroblasts; Transmigration