RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro
de Groot, J.
TNO Kwaliteit van Leven
Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristic, pathological invasive behaviour of these cells. FLS were obtained during joint replacement surgery. FLS were seeded in serum free medium with HMGB-1 or glycated albumin (BSA-AGE) on transwell filters coated with Matrigel. The lower compartment contained medium with serum as a chemoattractant. After three days, the percentage of invading cells was determined and compared to the control invasion. Stimulation with HMGB-1 increased invasiveness to 125% compared to the control (p = 0.001). Addition of anti-RAGE antibody reduced this back to baseline (98%, p = 0.002). Stimulation with BSA-AGE, another RAGE ligand, increased invasiveness to 150% compared to the control (p = 0.003). Addition of anti RAGE was again able to reduce the increased invasiveness back to baseline (95%, p = 0.008). HMGB-1 and BSA-AGE stimulated the invasiveness of RA-FLS by activation of RAGE. As such, RAGE may be an interesting target for therapy directed at the inhibition of synoviocyte activation. © Copyright Clinical and Experimental Rheumatology 2007.
To reference this document use:
advanced glycation end product
advanced glycation end product receptor
high mobility group B1 protein
in vitro study
Glycosylation End Products, Advanced
Clinical and Experimental Rheumatology, 25 (5), 740-742