Title
Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes
Author
TNO Kwaliteit van Leven
Steenvoorden, M.M.C.
Huizinga, T.W.J.
Verzijl, N.
Bank, R.A.
Ronday, H.K.
Luning, H.A.F.
Lafeber, F.P.J.G.
Toes, R.E.M.
de Groot, J.
Publication year
2006
Abstract
Objective. The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) could be one of these mechanisms. We undertook this study to investigate the role of the receptor for AGEs (RAGE) in mediating the cellular effects of AGEs on chondrocytes and fibroblast-like synoviocytes (FLS). Methods. AGE levels in human cartilage were determined by fluorescence, browning, and pentosidine levels. Chondrocyte activation by AGEs was assessed as the release of proteoglycans and the synthesis of matrix metalloproteinase 1 (MMP-1) and type II collagen messenger RNA (mRNA). The activation of FLS by AGEs was measured by MMP-1 production and invasion through matrix proteins. Results. Patients with focal degeneration of cartilage showed increased AGE levels in their healthy cartilage compared with the levels in healthy cartilage from donors without cartilage degeneration (P < 0.01 for both fluorescence and browning; P not significant for pentosidine content). Stimulation of bovine chondrocytes with glycated albumin increased the release of proteoglycans by 110% (P < 0.001) and the production of MMP-1 mRNA by 200% (P = 0.028). In addition, OA FLS produced 240% more MMP-1 when stimulated with glycated albumin (P < 0.001). Glycated matrix or albumin increased the catabolic activity of OA FLS, which was assessed as invasive behavior, by 150% and 140% (P = 0.001 and P = 0.010), respectively. Effects of stimulation with AGEs were blocked by a neutralizing antibody against RAGE, but not by an isotype control. Conclusion. This study shows that AGEs trigger RAGE on chondrocytes and FLS, leading to increased catabolic activity and therefore to cartilage degradation. AGEs, via RAGE, could therefore contribute to the development and/or progression of OA. © 2006, American College of Rheumatology. Chemicals / CAS: advanced glycation end product receptor, 198785-73-8, 247590-69-8; interstitial collagenase, 9001-12-1; pentosidine, 124505-87-9; advanced glycosylation end-product receptor; Glycosylation End Products, Advanced; Receptors, Immunologic.
Subject
Biomedical Research
advanced glycation end product
advanced glycation end product receptor
collagen type 2
glycosylated albumin
interstitial collagenase
matrix protein
messenger RNA
neutralizing antibody
pentosidine
adult
aged
aging
article
cartilage cell
cartilage degeneration
cartilage matrix
clinical article
controlled study
extracellular matrix
fibroblast
fluorescence
human
human cell
human tissue
osteoarthritis
priority journal
risk assessment
risk factor
statistical significance
synoviocyte
Cadaver
Chondrocytes
Fibroblasts
Glycosylation End Products, Advanced
Humans
Osteoarthritis
Receptors, Immunologic
Synovial Membrane
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http://resolver.tudelft.nl/uuid:de764aaa-08a2-4099-807b-2f4f92123573
DOI
https://doi.org/10.1002/art.21523
TNO identifier
239052
ISSN
0004-3591
Source
Arthritis and Rheumatism, 54 (54), 253-263
Document type
article