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Juha Risteli, Leila Risteli, Serum-Based Test of the Pathologic Breakdown of Type I Collagen Fibers, Clinical Chemistry, Volume 55, Issue 5, 1 May 2009, Pages 1032–1033, https://doi.org/10.1373/clinchem.2008.106674
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Featured Article: Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L. Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type-I collagen: a new serum marker of bone-collagen degradation. Clin Chem 1993;39:635–40.1
Our 1993 report described the in vitro production of a breakdown product of type I collagen that could be measured in human serum, which we called cross-linked carboxy-terminal telopeptide of type I collagen (ICTP),2 and characterized an immunoassay for monitoring it. We isolated the antigen from collagenase-treated demineralized femoral bone, identified it as the carboxy-terminal telopeptide of the collagen molecule, and showed that it contained an intermolecular cross-link. The corresponding antigen in the blood was homogeneous and cleared by the kidneys. We also referred to concomitant publications that suggested ICTP to be a good predictor of the clinical course of multiple myeloma and rheumatoid arthritis.
The project leading to the report was part of a research program that our group had designed more than 10 years earlier. There were 2 historical roots for our approach: the insight into protein chemistry and immunochemistry of collagens that we had gained as postdocs in Rupert Timpl’s laboratory in Martinsried, Germany, and the understanding of clinical chemistry that we acquired during residencies in the Laboratory of Oulu University Hospital, Finland. Our idea was to find a means for measuring the biosynthesis and breakdown rates of each of the major collagen types in the human body through the use of serum samples, so that the need for repeated tissue biopsies could be reduced. Considering that collagens are among the most abundant human proteins, it may seem strange that no such methods were available at the time. The only collagen-related method then generally known was the assay of urinary 4-hydroxyproline, which is specific for neither collagen nor collagen type. We first concentrated on the biosynthesis side to develop and commercialize assays for propeptide antigens that are freed from the biosynthetic precursors of type I collagen [carboxy-terminal propeptide of type I procollagen (PICP) (1) and amino-terminal propeptide of type I procollagen (PINP) (2)] and type III collagen [amino-terminal propeptide of type III procollagen (PIIINP) (3)]. Measurement of these propeptides allows estimation of synthesis rates in the same manner that C-peptide functions as an indicator of endogenous insulin production.
