hydroxylysine and pentosidine

The collagen network in human articular cartilage experiences a large number of stress cycles during life as it shows hardly any turnover after adolescence. We hypothesized that, to withstand fatigue failure, the physical condition of the collagen network laid down at adolescence is of crucial importance for the age of onset of osteoarthritis (OA).. We have compared the lysyl hydroxylation level and pyridinoline cross-link level of the collagen network of degenerated (DG) cartilage of the femoral knee condyle (representing a preclinical early stage of OA) with that of normal cartilage from the contralateral knee. The biological age of the collagen network was determined by means of pentosidine levels. For each donor, collagen modifications of normal cartilage were compared with DG cartilage that showed no significant remodeling of the collagen network (as evidenced by identical pentosidine levels).. DG cartilage contained significantly more hydroxylysine residues per collagen molecule in comparison with healthy cartilage from the same donor, both in the upper and lower half (the region near the articular surface and adjacent to bone, respectively). In addition, a significantly higher level of pyridinoline cross-linking was observed in the upper half of DG cartilage. Considering the biological age of the collagen network, the changes observed in DG cartilage must have been present several decades before cartilage became degenerated.. The data suggest that high levels of lysyl hydroxylation and pyridinoline cross-linking result in a collagen network that fails mechanically in long term loading. Areas containing collagen with low hydroxylysine and pyridinoline levels are less prone to degeneration. As such, this study indicates that post-translational modifications of collagen molecules synthesized during adolescence are causally involved in the pathogenesis of OA.

Topics: Aged; Aged, 80 and over; Amino Acids; Arginine; Case-Control Studies; Collagen; Cross-Linking Reagents; Humans; Hydroxylysine; Lysine; Middle Aged; Osteoarthritis, Knee

The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III, and IV) as well as controls. The amount of triple helical Hyl was increased in all patients. LP levels in OI were not significantly different; in contrast, the amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline level) was significantly increased. There was no relationship between the sum of pyridinolines and the amount of triple helical Hyl, indicating that lysyl hydroxylation of the triple helix and the telopeptides are under separate control. Cross-linking is the result of a specific three-dimensional arrangement of collagens within the fibril; only molecules that are correctly aligned are able to form cross-links. Inasmuch as the total amount of pyridinoline cross-links in OI bone is similar to control bone, the packing geometry of intrafibrillar collagen molecules is not disturbed in OI. Consequently, the brittleness of bone is not caused by a disorganized intrafibrillar collagen packing and/or loss of cross-links. This is an unexpected finding, because mutant collagen molecules with a random distribution within the fibril are expected to result in disruptions of the alignment of neighboring collagen molecules. Pepsin digestion of OI bone revealed that collagen located at the surface of the fibril had lower cross-link levels compared with collagen located at the inside of the fibril, indicating that mutant molecules are not distributed randomly within the fibril but are located preferentially at the surface of the fibril.

Topics: Adolescent; Adult; Amino Acids; Arginine; Biomarkers; Biopsy; Bone and Bones; Child; Child, Preschool; Collagen; Humans; Hydroxylysine; Infant; Lysine; Osteogenesis Imperfecta; Pepsin A; Pyridinium Compounds; Reference Values

To investigate age related and site specific variations in turnover and chemistry of the collagen network in healthy tendons as well as the role of collagen remodelling in the degeneration of the supraspinatus tendon (ST-D) in rotator cuff tendinitis.. Collagen content and the amount of hydroxylysine (Hyl), hydroxy-lysylpyridinoline (HP), lysylpyridinoline (LP), and the degree of non-enzymatic glycation (pentosidine) were investigated in ST-D and in normal human supraspinatus (ST-N) and biceps brachii tendons (BT-N) by high-performance liquid chromatography.. In BT-N, tendons that served as control tissue as it shows rarely matrix abnormalities, pentosidine levels rise linearly with age (20-90 years), indicating little tissue remodelling (resulting in an undisturbed accumulation of pentosidine). A similar accumulation was observed in ST-N up to 50 years. At older ages, little pentosidine accumulation was observed and pentosidine levels showed large interindividual variability. This was interpreted as remodelling of collagen in normal ST after age 50 years because of microruptures (thus diluting old collagen with newly synthesised collagen). All degenerate ST samples showed decreased pentosidine levels compared with age matched controls, indicating extensive remodelling in an attempt to repair the tendon defect. Collagen content and the amount of Hyl, HP, and LP of ST-N and BT-N did not change with age. With the exception of collagen content, which did not differ, all parameters were significantly (p < 0.001) lower in BT-N. The ST-D samples had a reduced collagen content and had higher Hyl, HP, and LP levels than ST-N (p < 0.001).. Inasmuch as Hyl, HP, and LP levels in ST-N did not change with age, tissue remodelling as a consequence of microruptures does not seem to affect the quality of the tendon collagen. On the other hand, the clearly different profile of post-translational modifications in ST-D indicates that the newly deposited collagen network in degenerated tendons is qualitatively different. It is concluded that in ST-D the previously functional and carefully constructed matrix is replaced by aberrant collagen. This may result in a mechanically less stable tendon; as the supraspinatus is constantly subjected to considerable forces this could explain why tendinitis is mostly of a chronic nature.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Amino Acids; Arginine; Child; Chronic Disease; Collagen; Cross-Linking Reagents; Humans; Hydroxylation; Hydroxylysine; Lysine; Middle Aged; Rotator Cuff; Tendinopathy

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 were low up to age 20 years, and increased linearly after this age. This indicates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supported by the finding that enzymatic modifications of collagen (hydroxylysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not related to age. The high remodelling is supported by levels of the crosslink lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (>20 years), whereas in young cartilage (<10 years) the opposite was seen; highest levels were close to the bone. LP levels in cartilage sections at age 14 years are high at the surface and close to the bone, but they are low in the middle region. This indicates that maturation of cartilage in the second decade of life starts in the upper half of the tissue, and occurs last in the tissue close to the bone. The effect of NEG products on instantaneous deformation of cartilage was investigated as a functional of topographical variations in pentosidine levels in vivo and in relation to in vitro induced NEG. Consistently, higher pentosidine levels were associated with a stiffer collagen network. A stiffer and more crosslinked collagen network may become more brittle and more prone to fatigue.

Topics: Adult; Aged; Aged, 80 and over; Aging; Arginine; Biomechanical Phenomena; Cartilage, Articular; Child; Child, Preschool; Collagen; Cross-Linking Reagents; Glycation End Products, Advanced; Humans; Hydroxylysine; Infant; Lysine; Middle Aged; Protein Processing, Post-Translational