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 c ollagen 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 take s place in vivo in bone, and the degree of racemization and isomerization o f CTx molecules may be an index of the biological age and the remodelling o f bone. The aim of the present study was to investigate the degree of racem ization and isomerization of type I collagen in human connective soft tissu es, 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 colla gen of arteries, lung, intestine, kidney, skeletal muscle and heart shows s ignificantly less racemization and isomerization than that of bone, suggest ing that these soft tissues have a faster turnover than bone. We also found that pyridinoline and, to a lesser degree, deoxypyridinoline are distribut ed throughout the different tissues investigated. Because bone type I colla gen is characterized by a high degree of both racemization/isomerization an d deoxypyridinoline crosslinking, the concomitant assessment of these two p osttranslational modifications is likely to result in a highly specific mar ker of bone resorption.