Title
RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro
Author
Steenvoorden, M.M.C.
Toes, R.E.M.
Ronday, H.K.
Huizinga, T.W.J.
de Groot, J.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
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.
Subject
Biomedical Research
Fibroblast-like synoviocyte
HMGB-1
Invasiveness
RAGE
Rheumatoid arthritis
advanced glycation end product
advanced glycation end product receptor
chemoattractant
glycosylated albumin
high mobility group B1 protein
ligand
matrigel
protein antibody
article
cell activation
cell function
cell invasion
controlled study
culture medium
fibroblast
human
human cell
in vitro study
joint prosthesis
priority journal
rheumatoid arthritis
serum
synovial fluid
synoviocyte
synovium
Antibodies, Anti-Idiotypic
Arthritis, Rheumatoid
Cell Movement
Cells, Cultured
Glycosylation End Products, Advanced
HMGB1 Protein
Humans
Receptors, Immunologic
Synovial Membrane
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TNO identifier
240172
ISSN
0392-856X
Source
Clinical and Experimental Rheumatology, 25 (5), 740-742
Document type
article