Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders

Abstract

Objective. To determine the content of two crosslinks, pyridinoline (a mature crosslink) and pentosidine (a senescent crosslink), in human articular cartilage, and to examine the effect of bone and joint disorders on the content 9f those crosslinks in articular cartilage.Methods. After pretreatment with SP-Sephadex C-25, high-performance liquid chromatography was conducted on a hydrolysate of human articular cartilage from 53 patients with one of the following diseases: osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, femoral head necrosis, and renal osteodystroResults. Pyridinoline levels were either unchanged with age or were slightly decreased in elderly patients. Pentosidine levels increased with age in the entire patient population. There was no significant difference in the pyridinoline content among the study groups, but there was a significant difference in pentosidine content (P < 0.001). ROD patients had the highest mean level of pentosidine (407 pmoleslmole of hydroxyproline), and RA patients had a higher mean P~Y (ROD). Conchsion. Bone and joint disorders do not affect the pyridinoline content in articular cartilage, but they do affect the pentosidine content.Pyridinoline is a trifunctional 3-hydroxypyridinium crosslink of mature collagen that is widely distributed in the connective tissues and is abundant in cartilage and bone (1,2). Pyridinoline is an intra-and inter-molecule crosslink of cartilage collagen fibrils and plays a role in stabilizing the collagen fibril network (3). It is a nonreducible crosslink, and its synthesis increases with collagen maturation. Urinary pyridinoline and its minor analog, deoxypyridinoline (4), have been used as markers of bone metabolism (5). It has also been proposed that these substances might reflect cartilage metabolism (6,7).Pentosidine, a condensation product of arginine, lysine, and ribose, is an end product of advanced glycation. Since it accumulates in human tissues with age, it is regarded as a senescent crosslink (8). It is also formed by sequential glycosylation and oxidation reactions. The accumulation of pentosidine in tissues such as the ocular lens and the skin increases in the presence of diabetic and uremic conditions (9). Plasma (1 0,ll) and urinary (12) levels of pentosidine have also been shown to be elevated under diabetic and uremic conditions.In previous studies characterizing human articular cartilage pentosidine by use of fluorometry and high-performance liquid chromatography (HPLC) of hydrolysates (13), we found that the amount of pentosidine increased exponentially with age. The amount of pyridinoline, however, remained constant with age

Advanced glycation end-products: a review

“…Histopathological studies have shown AGE accumulation in a variety of tissue types, including coronary atheroma, renal cortex, mesangium and glomerular basement membrane [12], as well as the dermal layer [13], amyloid plaques in Alzheimer's disease [14], cartilage in rheumatoid arthritis [15], cardiac muscle, lung and liver [16].…”

Effect of Age and Menopause on Serum Concentrations of Pentosidine, an Advanced Glycation End Product

“…It has been reported that pentosidine accumulated with age in tissues such as dura mater (1), lens (6), skin (17), cartilage (14,18), glomerular basement membrane (19), aorta (20), and meniscus (21). However, there have been few reports on the measurements of pentosidine in body fluids and on the age relationship of pentosidine therein.…”

Collagen crosslinks in fibromyalgia

“…Chromatographic methods are usually based on the determination of the crosslinks in urine, because higher concentrations of the metabolites are found in urine compared with other body fluids. The determination of pyridinium crosslinks has been described in serum and plasma (7,21), in cartilage (22), and in synovial fluid (23).…”