Carboxyterminal telopeptide structures of type I collagen in various human tissues
|Organizations:||University of Oulu, Faculty of Medicine, Institute of Diagnostics, Department of Clinical Chemistry
|Online Access:||PDF Full Text (PDF, 2.3 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:9789514262449
|Publish Date:|| 2010-08-10
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic dissertation to be presented with the assent of the Faculty of Medicine of the University of Oulu for public defence in the Great Hall of the Utsjoki Parish Hall (Pedar Jalven tie 1, Utsjoki), on 20 August 2010, at 12 noon
Professor Onni Niemelä
Professor Harri Suominen
Type I collagen is the main connective tissue protein in vertebrates. The cross-linking and correct organisation of the molecules is crucial for the proper function of the tissue. Traditionally collagen cross-linking has been studied using chemical cross-link analyses. However, this does not distinguish between the collagen types or the location of the cross-link within the molecule. The focus in this work was to study the carboxyterminal telopeptide domain of type I collagen for the differently cross-linked forms. An immunochemical approach was used and a new immunoassay, SP4, was developed for the detection of immaturely cross-linked peptide forms. The differently cross-linked structures were purified and characterised from human bone by using SP4 together with the earlier developed ICTP assay for trivalently cross-linked C-terminal telopeptide form. It was found that the majority of the trivalent cross-links in the C-terminal telopeptide were presently unknown structures, other than pyridinoline. A non-cross-linked form of C-terminal telopeptide of α1-chain of type I collagen was also discovered in bone. The epitope of the ICTP assay was characterised and found to reside in the phenylalanine rich region of the ICTP peptide. MMP-9, but not cathepsin K, mediated breakdown of the collagenous matrix was found to produce a peptide detectable by the ICTP assay.
Healthy human Achilles tendon comprises mainly of type I collagen. In ruptured Achilles tendons, an increased type III collagen content was found. Since the synthesis of type III collagen was not increased, it is postulated that the type III collagen must have accumulated over a long period of time indicative of a long-lasting microtraumatic process in the tendon before the total rupture occurred.
The ICTP content was increased and the ratio of SP4 to ICTP decreased in calcified stenotic aortic valves suggesting a change in the molecular organisation and cross-linking towards the type found in human bone. The total collagen content was dramatically decreased in the calcified valves.
Both in the Achilles tendons and in the aortic valves, the ICTP content was found to decrease with age with a concomitant increase in the variants of the C-terminal telopeptide structures detectable with the SP4 assay, pointing to a change in the molecular organisation of the collagenous matrix in these tissues.
Acta Universitatis Ouluensis. D, Medica
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