RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

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...

Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes

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...

The AGE of the matrix: Chemistry, consequence and cure

Accumulation of advanced glycation endproducts (AGEs) plays a crucial part in the development of age-related diseases and diabetic complications. AGEs are formed in vivo via the so-called Maillard reaction: a reducing sugar reacts with a protein to form a labile Amadori product that is subsequently stabilized, producing an irreversible, non...

Accumulation of Advanced Glycation End Products as a Molecular Mechanism for Aging as a Risk Factor in Osteoarthritis

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...

Advanced glycation end product ligands for the receptor for advanced glycation end products: Biochemical characterization and formation kinetics

Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown. Using standardized procedures and a variety of...

Ageing and osteoarthritis: A different perspective

Purpose of review: Across the world, osteoarthritis is the most commonly occurring musculoskeletal disease of the elderly, affecting more than 25% of the population older than 60 years of age. By far the single greatest risk factor for the development of osteoarthritis is age, but a mechanism to explain this relation has not yet been identified....

Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: A possible mechanism through which age is a risk factor for osteoarthritis

Objective. Age is an important risk factor for osteoarthritis (OA). During aging, nonenzymatic glycation results in the accumulation of advanced glycation end products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking on the stiffness of the collagen network in human articular cartilage. Methods. To increase AGE levels,...

Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage

Objective. To determine whether increasing advanced glycation end products (AGEs) in bovine articular cartilage to levels present in aged human cartilage modulates the tensile biomechanical properties of the tissue. Methods. Adult bovine articular cartilage samples were incubated in a buffer solution with ribose to induce the formation of AGEs...

Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: The use of pentosidine levels as a quantitative measure of protein turnover

During aging, non-enzymatic glycation results in the formation and accumulation of the advanced glycation endproduct pentosidine in long-lived proteins, such as articular cartilage collagen. In the present study, we investigated whether pentosidine accumulation also occurs in cartilage aggrecan. Furthermore, pentosidine levels in aggrecan...

Accumulation of advanced glycation end products decreases collagen turnover by bovine chondrocytes

The integrity of the collagen network is essential for articular cartilage to fulfill its function in load support and distribution. Damage to the collagen network is one of the first characteristics of osteoarthritis. Since extensive collagen damage is considered irreversible, it is crucial that chondrocytes maintain a functional collagen...

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage....

Effect of collagen turnover on the accumulation of advanced glycation end products

Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine. To test the hypothesis that this higher AGE...

Increase in the advanced glycation end product pentosidine in Bruch's membrane with age

PURPOSE. To determine whether there is an age-related increase of pentosidine in human Bruch's membranes and to localize pentosidine and carboxymethyllysine (CML), two well-characterized, advanced glycation end products (AGEs) in aged human Bruch's membranes and choroid in vivo. METHODS. Human Bruch's membrane samples were isolated from the...

Age-related decrease in proteoglycan synthesis of human articular chondrocytes: The role of nonenzymatic glycation

Objective. To examine the effect of nonenzymatic glycation of cartilage extracellular matrix on the synthetic activity of chondrocytes. Methods. The proteoglycan-synthesis rate (35SO42- incorporation) and levels of advanced nonenzymatic glycation (determined by high-performance liquid chromatography measurement of pentosidine) were evaluated in...

Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage: The age-related increase in Non-Enzymatic Glycation affects biomechanical properties of cartilage

A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. Here we investigate the accumulation of non-enzymatic glycation (NEG) products in healthy human articular cartilage, its relation to tissue remodelling and its role in tissue stiffening. Pentosidine levels...

Distinct associations of HbA(1c) and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus

Dysfunction of the vascular endothelium is considered an early step in the development of diabetic angiopathy. Hyperglycaemia results in endothelial dysfunction, both through direct effects of glucose and through formation of advanced glycosylation end-products (AGEs). We hypothesized that the effects of glucose and AGEs on endothelial function...