Search for new urinary biochemical markers of collagen degradation in man.
BACKGROUND
In the human body, collagen degradation produces various fragments released from the extracellular matrix, which end up in the urine as pyridinium cross-links, either free or bound to peptides or sugars.


METHODS
We developed a high-performance liquid chromatography (HPLC) technique, which measures not only free pyridinoline (Pyr) and deoxypyridinoline (Dpyr), but also glucosyl-galactosyl-pyridinoline (glc-gal-pyr) and four still unidentified bound pyridinolines. Assuming that in Paget's disease of bone and in growing children the cross-links (CL) mainly originate from bone tissue, whereas after spinal cord injury their high excretion rather reflects the degradation of non-osseous collagen, we compared the urinary output of seven different cross-links, among which four had not been described before.


RESULTS
Our results show that one of those, which we called CL1, is essentially originating from bone and is more specific in this respect than Dpyr, whereas glc-gal-pyr also reflects the degradation of non-osseous collagen. The best indicator of non-bone collagen degradation was CL3, one of the newly discovered cross-links.


CONCLUSIONS
In conclusion, we demonstrate that new sensitive pyridinoline cross-links can be identified and assayed in human urine and that their specificity helps to distinguish diseases related to bone collagen from those in which other forms of collagen are involved.
Roth
Marc
M
Department of Rheumatology and Institute of Physical Medicine, University Hospital, Gloriastrasse 25, CH-8091, Zurich, Switzerland.
Uebelhart
Daniel
D
D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000175:diagnosis; D010243:Paralysis / Q000652:urine; D013119:Spinal Cord Injuries / Q000175:diagnosis
D000596:Amino Acids; D015415:Biomarkers; C015484:pyridinoline; D003094:Collagen