Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: The role of advanced glycation end products

DeGroot, Jeroen; Verzijl, Nicole; Wijk, Marion J. G. Wenting-Van; Bank, Ruud A.; Lafeber, Floris P. J. G.; Bijlsma, J. W. J.; TeKoppele, J.M.

doi:10.1002/1529-0131(200111)44:11<2562::aid-art437>3.0.co;2-1

Cited by 114 publications

(79 citation statements)

References 60 publications

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“…Therefore, age-related changes in articular cartilage that influence the composition and strength of the cartilage matrix are very likely involved in the development of OA (55). One such change, the agerelated accumulation of AGEs, has previously been shown to increase tissue stiffness, decrease extracellular matrix turnover (synthesis and degradation), and affect many cellular processes (13,14,20,21,28,34,47,56). In the present study, we demonstrated in an in vivo model that this process of NEG is indeed causally involved in the age-related increase in susceptibility to OA.…”

Section: Discussionmentioning

confidence: 99%

“…Typically, 25-50 l of SF was collected from control joints and Ͼ150 l from experimental knees. Metalloproteinase activity in SF (final dilution 1:20 in 50 mM Tris [pH 7.5], 5 mM CaCl 2 , 150 mM NaCl, 1 M ZnCl 2 , 0.01% Brij-35, 0.02% NaN 3 ) was determined with fluorogenic substrate TNO211-F (5 M) in the presence of an EDTA-free general proteinase inhibitor (Complete; Roche, Indianapolis, IN) (47,48). This assay is considered to represent overall metalloproteinase activity.…”

Section: Methodsmentioning

confidence: 99%

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Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis

DeGroot¹,

Verzijl²,

Wijk

et al. 2004

Arthritis & Rheumatism

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181

114

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Objective. Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. Its etiology is largely unknown, but age is the most prominent risk factor. The current study was designed to test whether accumulation of advanced glycation end products (AGEs), which are known to adversely affect cartilage turnover and mechanical properties, provides a molecular mechanism by which aging contributes to the development of OA.Methods. The hypothesis that elevated AGE levels predispose to the development of OA was tested in the canine anterior cruciate ligament transection (ACLT) model of experimental OA. Cartilage AGE levels were enhanced in young dogs by intraarticular injections of ribose. This mimics the accumulation of AGEs without the interference of other age-related changes. The severity of OA was then assessed 7 weeks after ACLT surgery in dogs with normal versus enhanced AGE levels.Results. Intraarticular injections of ribose enhanced cartilage AGE levels ϳ5-fold, which is similar to the normal increase that is observed in old dogs. ACLT surgery resulted in more-pronounced OA in dogs with enhanced AGE levels. This was observed as increased collagen damage and enhanced release of proteoglycans. The attempt to repair the matrix damage was impaired; proteoglycan synthesis and retention were decreased at enhanced AGE levels. Mankin grading of histology sections also revealed more-severe OA in animals with enhanced AGE levels.Conclusion. These findings demonstrate increased severity of OA at higher cartilage AGE levels and provide the first in vivo experimental evidence for a molecular mechanism by which aging may predispose to the development of OA.The population of Western society is aging rapidly. Consequently, age-related diseases will increase greatly over the coming decades and will have a great impact on the quality of life of the elderly. Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly and poses a significant public health problem (1). The most prominent feature of OA is the progressive destruction of articular cartilage, resulting in impaired joint motion, severe pain, and, ultimately, disability (2). As yet, the etiology of OA remains largely unknown. The incidence of OA increases with age: Ͼ50% of the population over 60 years of age is affected (3,4). Although age is identified as the main risk factor for the development of OA, the mechanism by which aging is involved remains unclear. Age-related changes in the articular cartilage are expected to play an important role in the susceptibility of cartilage to OA.Articular cartilage derives its mechanical properties from its extracellular matrix. This matrix is composed of type II collagen, which forms a 3-dimensional network that provides the cartilage with resistance to tensile forces (5).

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis

DeGroot¹,

Verzijl²,

Wijk

et al. 2004

Arthritis & Rheumatism

Self Cite

181

114

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“…Recently, an increase in advanced glycation end products was shown to result in decreased cartilage degradation by MMPs (24). Thus, it has been suggested that the level of cartilage glycation may influence the progression of degradation.…”

Section: Discussionmentioning

confidence: 99%

Synovial fluid exoglycosidases are predictors of rheumatoid arthritis and are effective in cartilage glycosaminoglycan depletion

Ortutay

Polgar

Gömör³

et al. 2003

Arthritis & Rheumatism

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Objective. To analyze enzymes involved in joint damage by simultaneous investigation of glycosidases and matrix metalloproteinases (MMPs) in patients with various joint diseases. In joint diseases, the major clinical symptoms and disability of patients are caused by an irreversible destruction of hyaline cartilage. Enzymes capable of degrading extracellular matrix components (collagen and aggrecan) and concomitantly exposing chondrocytes to a variety of cytotoxic and/or apoptosis-inducing factors are considered to be the major effector molecules in cartilage degradation. Methods. Activities of glycosidases (␤-DRecently, significant advances have been made in our understanding of joint destruction and the mechanism of proteolytic cleavage of cartilage. Active proteases are currently implicated in the destructive processes and include matrix metalloproteinases (MMPs), the ADAM family (1), the ADAM-TS family (2), and serine proteases (elastase, cathepsins, and granzymes) (3-5). Of the 4 groups of MMPs, collagenase (MMP-1 in particular) appears to be responsible for the degradation of interstitial collagens. The gelatinases (including MMP-2 and MMP-9) degrade the denatured form of collagens, thus acting in synergy with MMP-1. The stromelysins (including MMP-3) have a broader substrate specificity for non-connective tissue components.

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“…Broad-spectrum MMP activity was determined in 71 out of 73 CRC patient samples (in two cases insufficient sample was left after zymography to perform the activity assay) using the quenched fluorogenic peptide substrate TNO211-F (Dabcyl-Gaba-Pro-GlnGly-Leu-Cys(Fluorescein)-Ala-Lys-NH 2 ) essentially as described previously (Beekman et al, 1999;DeGroot et al, 2001). The substrate is mainly cleaved by the gelatinases (MMP-2 and -9) and collagenase 3 (MMP-13) and to a lesser extent by collagenase 2 (MMP-8) and membrane-bound metalloproteinase (MT1 -MMP).…”

Section: Fluorometric Mmp Activity Assaymentioning

confidence: 99%

Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer

Waas

Lomme

DeGroot³

et al. 2002

Br J Cancer

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The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a limited (n=33) number of patients. Broad-spectrum matrix metalloproteinase activity and both the active and latent forms of the gelatinases matrix metalloproteinase-2 and -9 were higher in tumour than in normal mucosa. The ratio's between active and latent forms of matrix metalloproteinase-2 and -9 were highest in tumour tissue and normal mucosa, respectively. Matrix metalloproteinase-2 levels, both active and latent forms, correlated inversely with stage of disease, the tumours without synchronous distant metastases containing significantly (P=0.005) more active matrix metalloproteinase-2 than the others. At much lower levels of activity, the same trend was observed in distant normal mucosa. The level of latent form of matrix metalloproteinase-9 in tumour depended on tumour location. Neither the active form of matrix metalloproteinase-9 nor broad-spectrum matrix metalloproteinase activity in tumour tissue did correlate with any of the clinicopathological parameters investigated. The results demonstrate explicit differences between the activity of matrix metalloproteinase-2 and -9, indicating different roles for both gelatinases in tumour progression. Such data are necessary in order to develop rational anti-cancer therapies based on inhibition of specific matrix metalloproteinases.

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Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: The role of advanced glycation end products

Cited by 114 publications

References 60 publications

Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis

Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis

Synovial fluid exoglycosidases are predictors of rheumatoid arthritis and are effective in cartilage glycosaminoglycan depletion

Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer

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