Collagen structure regulates fibril mineralization in osteogenesis as revealed by cross-link patterns in calcifying callus

Although >80% of the mineral in mammalian bone is present in the collagen f ibrils, limited information is available about factors that determine a pro per deposition of mineral. This study investigates whether a specific colla gen matrix is required for fibril mineralization, Calcifying callus from do g tibias was obtained at various times (3-21 weeks) after fracturing, At 3 weeks, hydroxylysine (Hyl) levels were almost twice as high as in control b one, gradually reaching normal levels at 21 weeks, The decrease in Hyl leve ls can only be the result of the formation of a new collagen network at the expense of the old one,The sum of the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in callus matched that of bone at all stag es of maturation, However, the ratio HP/LP was 2.5-4.5 times higher in call us at 3-7 weeks than in normal bone and was normalized at 21 weeks. Some 40 % of the collagen was nonmineralized at the early stages of healing, reachi ng control bone values (approximate to 10%) at 21 weeks, In contrast, only a small increase in callus mineral content from 20.0 to 22.6 (% of dry tiss ue weight) from week 3 to 21 was seen, indicating that initially a large pr oportion of the mineral was deposited between, and not within, the fibrils, A strong relationship (r = 0.80) was found between the ratio HP/LP and fib ril mineralization; the lower the HP/LP ratio, the more mineralized the fib rils were, Because the HP/LP ratio is believed to be the result of a specif ic packing of intrafibrillar collagen molecules, this study implies that mi neralization of fibrils is facilitated by a specific orientation of collage n molecules in the fibrils.