Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Matrix Components Influence the Aggressive Behavior of Rheumatoid Arthritis Synovial Fibroblasts.
Lefevre2, Stephanie, Zimmermann3, Birgit, Geyer3, Matthias, Lehr5, Angela, Sturz4, Henning, Steinmeyer1, Jürgen, Rehart5, Stefan
Dept Experimental Orthopedics, Justus-Liebig-University Giessen
Dept Internal Medicine and Rheumatology, Justus-Liebig University Giessen, Bad Nauheim, Germany
Dept Internal Medicine and Rheumatology, Justus-Liebig University Giessen
Dept Orthopedics and Orthopedic Surgery, Justus-Liebig-University Giessen
Dept Orthopedics and Trauma Surgery, Markus-Hospital Frankfurt
Central mediators in joint destruction in rheumatoid arthritis (RA) are activated synovial fibroblasts (SFs). They adhere to and invade into human cartilage but the molecular details of this disease-specific behavior are known only to a limited extent. As we could show the migratory potential of RASFs in the SCID mouse model of RA, in the present study we addressed the role of extracellular matrix (ECM) regarding RASF adhesion and migration.
Chemotactic effects of finely ground cartilage were analyzed in vitro. After (membrane-) coating with Matrigel, growth factor-reduced Matrigel or collagen type II and adding RASFs, adhesion (after 30min) and transmigration (after 16h) of RASFs were analyzed. Isolated RASFs or whole synovial RA tissue were coimplanted with healthy human cartilage (ipsilateral; I) subcutaneously into SCID mice. Cartilage without RASFs was inserted contralaterally (Co). To analyze potential effects of the ECM, bovine or murine cartilage or cartilage without vital chondrocytes was implanted. ECM components were analyzed in vivo by coating the carrier matrices in various combinations (either the ipsilateral or the contralateral carrier matrix or both) with the following factors: Matrigel, fibronectin, aggrecan, growth factor-reduced Matrigel, collagen type II, PuraMatrix Peptide Hydrogel. Histological analyses of implants followed after 60 days.
RASFs invaded the coimplanted cartilage directly and migrated to and invaded into the cartilage inserted contralaterally independent of the species background and the source of RASFs (isolated or whole RA synovium). Cartilage inserted into carrier matrices coated with growth factor-reduced Matrigel showed a reduced invasion (invasion score I (non-coated carrier-matrix): 1.7±0.5, Co (coated carrier matrix): 0.2±0.3; I (coated carrier matrix): 0.9±0.6, Co (non-coated carrier matrix): 2.0±0) compared to cartilage in uncoated matrices (control; I: 2.1±0.6; Co: 1.5±0.4). A concentration-dependent increase of the chemotactic effect of finely ground cartilage regarding RASF migration was demonstrated in vitro. Transmigration and adhesion of RASFs were decreased in vivo after coating with growth factor-reduced Matrigel compared to coating with Matrigel or collagen type II (up to 86fold or 49fold resp.).
The ECM as well as matrix associated components such as growth factors influence RASF migration from the ipsilaterally to the contralaterally implanted cartilage. Accordingly, adhesion of RASFs to growth factor-reduced Matrigel was decreased compared to other coatings. In contrast, chondrocyte vitality and species background of the cartilage appear not to be crucial for RASF migration. Taken together, matrix components play a central role in RASF migration, transmigration, adhesion to cartilage and following joint destruction.
To cite this abstract, please use the following information:
Lefevre, Stephanie, Zimmermann, Birgit, Geyer, Matthias, Lehr, Angela, Sturz, Henning, Steinmeyer, Jürgen, et al; Matrix Components Influence the Aggressive Behavior of Rheumatoid Arthritis Synovial Fibroblasts. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1722