Cross-linking and the molecular packing of corneal collagen.

We have quantitatively characterized, for the first time, the cross-linking in bovine cornea collagen as a function of age. The major iminium reducible cross-links were dehydro-hydroxylysinonorleucine (deH-HLNL) and dehydro-histidinohydroxymerodesmosine (deH-HHMD). The former rapidly diminished after birth; however, the latter persisted in mature animals at a level of 0.3 - 0.4 moles/mole of collagen. A nonreducible cross-link, histidinohydroxylysinonorleucine (HHL), previously found only in skin, was also found to be a major mature cross-link in cornea. The presence of HHL indicates that cornea fibrils have a molecular packing similar to skin collagen. However, like deH-HHMD, the HHL content in corneal fibrils only reaches a maximum value with time about half that of skin. These data suggest that the corneal fibrils are comprised of discrete filaments that are internally stabilized by HHL and deH-HHMD cross-links. This pattern of intermolecular cross-linking would facilitate the special collagen swelling property required for corneal transparency.

Cross-linking and new bone collagen synthesis in immobilized and recovering primate osteoporosis.

Quantification of collagen cross-links of monkey bone (tibia), from various time periods of immobilization (up to 7 months) and their subsequent reambulation (up to 40 months) was determined. Results indicated reducible cross-link concentrations markedly increased and peaked at the seven-month period of immobilization and returned to control values after 40 months of recovery. Chromatographic profiles of the major cross-linked peptides indicated that the increased cross-linking after seven months immobilization occurred between residue Hylald-16c as well as Lysald-16c of the alpha 1 chains and residue 87 Hyl of alpha chains of type I collagen. Mature, stable cross-link concentrations as well as their molecular loci remained constant throughout immobilization and reambulation. These results strongly suggest that rapid new bone collagen synthesis occurred during the osteoporotic state due to immobilization. With long-term recovery, the rate of collagen synthesis apparently returned to match the control bone.