Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover.
Urinary excretion of the type I collagen C-telopeptide (CTx) has been shown to be a sensitive index of the rate of bone resorption. The human type I collagen sequence A(1209)HDGGR(1214) of CTx can undergo racemization of the aspartic acid residue Asp(1211) and isomerization of the bond between this residue and Gly(1212). These spontaneous non-enzymic chemical reactions takes place in vivo in bone, and the degree of racemization and isomerization of CTx molecules may be an index of the biological age and the remodelling of bone. The aim of the present study was to investigate the degree of racemization and isomerization of type I collagen in human connective soft tissues, in order to estimate the rate of collagen turnover in adult tissues and compare it with that of bone. We also performed a systematic evaluation of the pyridinium cross-link content in adult human tissues. Using antibodies raised against the different CTx forms, we found that bone and dermis are the tissues that show most racemization and isomerization. The type I collagen of arteries, lung, intestine, kidney, skeletal muscle and heart shows significantly less racemization and isomerization than that of bone, suggesting that these soft tissues have a faster turnover than bone. We also found that pyridinoline and, to a lesser degree, deoxypyridinoline are distributed throughout the different tissues investigated. Because bone type I collagen is characterized by a high degree of both racemization/isomerization and deoxypyridinoline cross-linking, the concomitant assessment of these two post-translational modifications is likely to result in a highly specific marker of bone resorption.
Gineyts
E
E
INSERM U403, Hôpital E.Herriot, pavillon F, place d'Arsonval, 69437 Lyon cedex 03, France. gineyts@lyon151.inserm.fr
Cloos
P A
PA
Borel
O
O
Grimaud
L
L
Delmas
P D
PD
Garnero
P
P
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003238:Connective Tissue / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry; D005260:Female; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D003432:Cross-Linking Reagents; D010446:Peptide Fragments; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen