Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis
Open Access
- 5 April 2004
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 50 (4), 1207-1215
- https://doi.org/10.1002/art.20170
Abstract
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 ∼5-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.Keywords
This publication has 65 references indexed in Scilit:
- Steady progression of osteoarthritic features in the canine groove modelOsteoarthritis and Cartilage, 2002
- The canine ‘groove’ model, compared with the ACLT model of osteoarthritisOsteoarthritis and Cartilage, 2002
- Accumulation of Advanced Glycation End Products Decreases Collagen Turnover by Bovine ChondrocytesExperimental Cell Research, 2001
- 1998 Steindler award lecture. Is collagen fatigue failure a cause of osteoarthrosis and prosthetic component migration? A hypothesisJournal of Orthopaedic Research, 1999
- Breaking the curse of the AGEsNature, 1996
- Diabetic and age-related enhancement of collagen-linked fluorescence in cortical bones of ratsLife Sciences, 1994
- Relation between Complications of Type I Diabetes Mellitus and Collagen-Linked FluorescenceNew England Journal of Medicine, 1986
- Role of synovial membrane inflammation in cartilage matrix breakdown in the Pond‐Nuki dog model of osteoarthritisArthritis & Rheumatism, 1985
- Thermal stability, mechanical properties and reducible cross-links of rat tail tendon in experimental diabetesBiochimica et Biophysica Acta (BBA) - General Subjects, 1981
- Fatigue of Articular CartilageNature, 1973