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 fibrils, limited information is available about factors that determine a proper deposition of mineral. This study investigates whether a specific collagen matrix is required for fibril mineralization. Calcifying callus from dog 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 bone, gradually reaching normal levels at 21 weeks. The decrease in Hyl levels 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 stages of maturation. However, the ratio HP/LP was 2.5-4.5 times higher in callus 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, reaching control bone values (approximately 10%) at 21 weeks. In contrast, only a small increase in callus mineral content from 20.0 to 22.6 (% of dry tissue weight) from week 3 to 21 was seen, indicating that initially a large proportion 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 fibril mineralization; the lower the HP/LP ratio, the more mineralized the fibrils were. Because the HP/LP ratio is believed to be the result of a specific packing of intrafibrillar collagen molecules, this study implies that mineralization of fibrils is facilitated by a specific orientation of collagen molecules in the fibrils.
Wassen
M H
MH
Gaubius Laboratory TNO Prevention and Health, Leiden, The Netherlands.
Lammens
J
J
Tekoppele
J M
JM
Sakkers
R J
RJ
Liu
Z
Z
Verbout
A J
AJ
Bank
R A
RA
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D002146:Bony Callus / Q000502:physiology*; D002113:Calcification, Physiologic / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D004285:Dogs; D050723:Fractures, Bone / Q000503:physiopathology*; D006901:Hydroxylysine / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D011489:Protein Denaturation; D013977:Tibia / Q000502:physiology; D013997:Time Factors
D000596:Amino Acids; D006901:Hydroxylysine; C015484:pyridinoline; D003094:Collagen; D008239:Lysine; D002118:Calcium