Background In rheumatoid arthritis (RA), aggressive synovial fibroblasts (SFs) play a central role in cartilage destruction and the spreading of the disease based on a long-distance migratory potential in vivo. In this setting, the adhesion of RASFs to extracellular matrix (ECM) is a central feature required for subsequent cartilage invasion. Therefore, effects of ECM-associated growth factors on the adhesion of fibroblasts from different rheumatic diseases were examined.
Methods Healthy human cartilage was implanted into SCID mice together with RASFs (ipsilateral). At the contralateral flank, cartilage without cells was implanted. To analyze different matrix components, the ipsilateral, the contralateral or both carrier matrices of the implanted cartilage were coated with Matrigel® (MG) or growth factor-reduced Matrigel® (GFR MG). After 60 days, the implants were analyzed. In vitro, multi-well culture plates were coated with MG, GFR MG, or remained untreated, respectively. Furthermore, TGF-βand/or PDGF were added to GFR MG according to concentrations present in MG. Cellular adhesion of 5×103 added RASFs, osteoarthritis (OA) SFs or systemic sclerosis (SSc) dermal fibroblasts (all n=4) was analyzed after 15 min.
Results When cartilage was embedded into carrier matrices coated with GFR MG in the SCID mouse model of RA, a reduced RASF invasion compared to cartilage in MG-coated or non-coated carrier matrices was observed.In general, an increased adhesion was visible in vitro after multi-well plate coating with GFR MG or MG. By using GFR MG, a reduction of cellular adhesion (1.3fold) of RASFs was observed in comparison to wells coated with MG. In contrast, SFs and dermal fibroblasts from OA and SSc patients showed an increased adhesion to GFR MG compared to MG (OA: 1.9fold; SSc: 2.1fold). After adding TGF-β or PDGF to GFR MG, RASFs showed an increased adhesion to GFR/TGF-β (1.4fold) and an almost equal adhesion to GFR/PDGF (1.1fold) compared to MG. SSc dermal fibroblasts and OASFs showed a decreased adhesion to these matrices compared to GFR alone (SSc: GFR/TGF-β: 1.02fold, GFR/PDGF: 1.23fold; OA: GFR/TGF-β: 1.2fold, GFR/PDGF: 1.5fold). By adding a mix of TGF-β and PDGF to GFR, a reduced adhesion was visible especially for SSc dermal fibroblasts and OASFs in comparison to all other matrices analyzed.
Conclusions The data demonstrate that the ECM and its associated components, e.g. growth factors, seem to play a critical role in RASF attraction and adhesion to cartilage. These factors are able to activate different adhesion molecules in RASFs. RASFs are characterized by increased and distinct surface expression of adhesion molecules and differ from fibroblasts of other diseases. Therefore, the observed behavior of RA synovial fibroblasts regarding adhesion to growth factor-containing matrix appears to be a disease-specific property.
Disclosure of Interest None Declared
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