Journal article

Publication year: 2017

Pages: 4588-4595

Journal: The Journal of Immunology

Volume number: 198

Issue number: 12

ISSN: 0022-1767

eISSN: 1550-6606

DOI Link: https://doi.org/10.4049/jimmunol.1600989

Publisher: American Association of Immunologists

Abstract: 
In rheumatoid arthritis (RA), cartilage and bone matrix are degraded, and extracellular matrix (ECM) proteins, acting as cellular activators, are liberated. Similar to ECM proteins, matrix-bound chemokines, cytokines, and growth factors (GFs) influence functional properties of key cells in RA, especially synovial fibroblasts. The role of these molecules on attachment, migration, and proinflammatory and prodestructive activation of RASFs was analyzed. Adhesion/migration of RASFs were examined under GF-enriched (GF(+)) or -reduced (GF(-)) conditions with or without addition of matrix-associated GFs, TGF-beta, and plateletderived GF to GF 2 or culture supernatants. Fibroblast adhesion and alterations in proinflammatory/prodestructive properties (e.g., IL-6/matrix metalloproteinase 3-release) in response to matrix-associated molecules were compared. Effects of GF+, GF 2, and other ECM components on human RASF-mediated cartilage invasion were examined in the SCID mouse model. RASF adhesion under GF(-) conditions was significantly lower compared with GF(+) conditions (6.8-versus 8.3-fold). This effect was specific for RA because control cells showed opposite effects (e.g., osteoarthritis synovial fibroblasts [SF]; GF(-) versus GF+: 10.7-versus 8-fold). Addition of TGF-beta to GF(-) increased RASF attachment (12.7-fold) compared with other matrices and components. RASF adhesion to GF(+) matrix resulted in the strongest IL-6 and matrix metalloproteinase-3 release, and was even more pronounced compared with supplementation of single GFs. In vivo, GF(-) matrix decreased RASF-mediated cartilage invasion compared with GF(+) matrix. ECM components and especially GFs when bound within ECM actively enhance RASF attraction and cartilage adhesion. This observation was specific for RASFs as a reverse behavior was observed for controls.

Harvard Citation style: Lefevre, S., Schwarz, M., Meier, F., Zimmermann-Geller, B., Tarner, I., Rickert, M., et al. (2017) Disease-Specific Effects of Matrix and Growth Factors on Adhesion and Migration of Rheumatoid Synovial Fibroblasts, The Journal of Immunology, 198(12), pp. 4588-4595. https://doi.org/10.4049/jimmunol.1600989

APA Citation style: Lefevre, S., Schwarz, M., Meier, F., Zimmermann-Geller, B., Tarner, I., Rickert, M., Steinmeyer, J., Sauerbier, M., Rehart, S., Mueller-Ladner, U., & Neumann, E. (2017). Disease-Specific Effects of Matrix and Growth Factors on Adhesion and Migration of Rheumatoid Synovial Fibroblasts. The Journal of Immunology. 198(12), 4588-4595. https://doi.org/10.4049/jimmunol.1600989