Lysine Hydroxylation Of Collagen Research Articles

Characterization of the bone matrix and its contribution to tooth loss in human cadaveric mandibles

Objective. It is uncertain as to what extent the major bone matrix constituents, mineral and collagen, show inter-individual variation and dependence on age and sex in jawbones. The purpose of this study was to clarify this uncertainty using cadaveric mandibles and investigate the association of bone matrix with the number of existing teeth. Materials and methods. Cortical bone samples (1 × 1 cm) collected from the mental of 48 cadaveric mandibles (27 men and 21 women; age range = 56–93 years and 63–103 years, respectively) were used to quantify three bone matrix indices: mineral content, collagen content and extent of lysine hydroxylation of collagen. Associations with age and comparisons by sex were evaluated based on bone matrix indices and the numbers of existing teeth. The numbers of existing teeth were compared between the groups showing low and high bone matrix index values. Results. A great amount of inter-individual variation was seen in all bone matrix indices. No bone matrix indices were associated with age, while the number of existing teeth was negatively associated with age. The bone matrix indices and number of existing teeth did not differ by sex. The number of existing teeth was nearly twice as high in the group showing high collagen content as in the low collagen group; however, an analysis of covariance showed a significant inter-group difference not from bone matrix indices, but rather from age. Interestingly, in comparison to femoral collagen, mandibular collagen showed lower lysine hydroxylation, which can represent an aspect of bone quality. Conclusions. Mandibular bone matrix shows great inter-individual variation and is independent of age and sex, but did not show as strong a relationship with tooth loss as age. Even so, mandibular collagen may represent a unique characteristic of bone matrix and deserves to be further investigated.

Characterization of Mandibular Bones in Senile Osteoporotic Mice

At present, little is known about the age-related changes in jaw bones. The aim of this study was to characterize the mandibles of 6 month-old senile osteoporotic mice, SAMP6, and compare with those of age-matched controls, SAMR1. In comparison to SAMR1, SAMP6 showed thinner cortical bone, lower bone volume, and poorly organized collagen matrix. The collagen fibril diameter in SAMP6 was significantly smaller than that of SAMR1. In SAMP6 both collagen content and cross-links were lower than those of SAMR1, but the ratio of the major mature cross-link (pyridinoline) to its precursor reducible cross-link (dehydrodihydroxylysinonorleucine/its ketoamine) was higher in comparison to SAMR1. In addition, the extent of lysine hydroxylation of collagen was higher in SAMP6 than that of SAMR1. These results indicate that not only the quantity of collagen but also its quality are altered in SAMP6 and may result in the age-associated osteoporotic defects of mandibles.

Lysine hydroxylation of collagen in a fibroblast cell culture system

The lysine (Lys) hydroxylation pattern of type I collagen produced by human fibroblasts in culture was analyzed and compared. Fibroblasts were cultured from normal human skin (NSF), keloid (KDF), fetal skin (FDF), and skin tissues of Ehlers–Danlos syndrome type VIA and VIB patients (EDS-VIA and -VIB). The type I collagen α chains with or without non-helical telopeptides were purified from the insoluble matrix and analyzed. In comparison with NSFs, KDF and FDF showed significantly higher Lys hydroxylation, particularly in the telopeptide domains of both α chains. Both EDS-VIA and -VIB showed markedly lower Lys hydroxylation in the helical domains of both α chains whereas that in the telopeptides was comparable with those of NSFs. A similar profile was observed in the tissue sample of the EDS-VIB patient. These results demonstrate that the Lys hydroxylation pattern is domain-specific within the collagen molecule and that this method is useful to characterize the cell phenotypes in normal/pathological connective tissues.

Changes in collagen cross-link ratios in bone and urine of guinea pigs fed graded dietary vitamin C: a functional index of vitamin C status

Vitamin C is essential for the hydroxylation of lysine in collagen. The resulting hydroxylysine residues, together with the precursor lysine residues, are then incorporated into the stable collagen cross-links: pyridinoline and deoxypyridinoline. A reduction in lysine hydroxylation, resulting from an inadequate supply of vitamin C, might decrease the ratio of the pyridinoline crosslinks to the deoxypyridinoline crosslinks. This hypothesis was tested in a guinea pig model, using a purified diet providing vitamin C in the following amounts: (a) 0.5 mg/day; (b) 1 mg/day; (c) 5 mg/day; (d) 0.25% w/v in the diet (providing 49 mg/day); (e) 1.0% w/v (providing 205 mg/day); or (f) 5.0% w/v (providing 1128 mg/day). Weanling male guinea pigs each received one of these diets for 46 days, after which their tissue vitamin C concentrations, and the concentrations of hydroxyproline, pyridinoline, and deoxypyridinoline in bone, and of creatinine, pyridinoline, and deoxypyridinoline in urine, were measured. The ratio of pyridinoline to deoxypyridinoline in bone collagen and in urinary collagen fragments decreased significantly as vitamin C depletion became more severe. Animals receiving the higher intakes of vitamin C grew more rapidly than did those receiving the lower intakes, but the relationship between vitamin C intake and the collagen crosslinks ratio remained highly significant, even after adjusting for intergroup differences in growth rates. Thus, the ratio between the two collagen crosslinks could provide a specific and sensitive functional index of vitamin C in animals and man. This is an important goal, in view of the need to be able to define optimum intakes of vitamin C.