Title
Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: The role of advanced glycation end products
Author
de Groot, J.
Verzijl, N.
Wenting-Van Wijk, M.J.G.
Bank, R.A.
Lafeber, F.P.J.G.
Bijlsma, J.W.J.
Tekoppele, J.M.
Gaubius Instituut
Publication year
2001
Abstract
Objective. Progressive destruction of articular cartilage is a hallmark of osteoarthritis (OA) and rheumatoid arthritis (RA). Age-related changes in cartilage may influence tissue destruction and thus progression of the disease. Therefore, the effect of age-related accumulation of advanced glycation end products (AGEs) on cartilage susceptibility to proteolytic degradation by matrix metalloproteinases (MMPs) present in synovial fluid (SF) of OA and RA patients was studied. Methods. Cartilage was incubated with APMA-activated SF obtained from OA or RA patients, and tissue degradation was assessed by colorimetric measurement of glycosaminoglycan (GAG) release. Cartilage degradation was related to the level of AGEs in cartilage from donors of different ages (33-83 years) and in cartilage with in vitro-enhanced AGE levels (by incubation with ribose). MMP activity in SF was measured using a fluorogenic substrate. AGE levels were assessed by high-performance liquid chromatography measurement of the glycation product pentosidine. Results. In cartilage from donors ages 33-83 years, a strong correlation was found between the age-related increase in pentosidine and the decrease in MMP-mediated tissue degradation (r = -0.74, P < 0.0005). Multiple regression analysis showed pentosidine to be the strongest predictor of the decreased GAG release (P < 0.0005); age did not contribute (P > 0.8). In addition, decreased MMP-mediated GAG release was proportional to increased pentosidine levels after in vitro enhancement of glycation (r = -0.27, P < 0.01). This was demonstrated for both OA and RA SF (for control versus glycated, P < 0.002 for all SF samples tested). Conclusion. Increased cartilage AGEs resulted in decreased cartilage degradation by MMPs from SF, indicating that aged cartilage is less sensitive than young cartilage to MMP-mediated cartilage degradation, such as occurs in OA and RA. Therefore, the level of cartilage glycation may influence the progression of these diseases.
Subject
Health Biology
Biomedical Research
glycosaminoglycan
matrix metalloproteinase
pentosidine
adult
aged
article
articular cartilage
cartilage degeneration
clinical article
colorimetry
controlled study
disease course
female
high performance liquid chromatography
human
male
osteoarthritis
priority journal
protein degradation
rheumatoid arthritis
synovial fluid
Adult
Aged
Aged, 80 and over
Aging
Animals
Arginine
Arthritis, Rheumatoid
Cartilage, Articular
Cattle
Chromatography, High Pressure Liquid
Glycosaminoglycans
Humans
Knee Joint
Lysine
Matrix Metalloproteinases
Middle Aged
Osteoarthritis, Knee
Phenylmercuric Acetate
Ribose
Synovial Fluid
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DOI
https://doi.org/10.1002/1529-0131(200111)44:11<2562::aid-art437>3.0.co;2-1
TNO identifier
236285
ISSN
0004-3591
Source
Arthritis and Rheumatism, 44 (11), 2562-2571
Document type
article