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Oulun yliopiston väitöskirjat

CARBOXYTERMINAL TELOPEPTIDE STRUCTURES OF TYPE I COLLAGEN IN VARIOUS HUMAN TISSUES, ACTA UNIVERSITATIS OULUENSIS D Medica 1062

ISBN-13:	978-951-42-6243-2
Kieli:	englanti
Kustantaja:	Oulun yliopisto
Oppiaine:	Lääketiede, farmasia
Painosvuosi:	2010
Sidosasu:	pehmeäkantinen
Sijainti:	Print Tietotalo
Sivumäärä:	126
Tekijät:	ERIKSEN HEIDI

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Type I collagen is the main connective tissue protein in vertebrates. The cross-linking and correctorganisation of the molecules is crucial for the proper function of the tissue. Traditionally collagencross-linking has been studied using chemical cross-link analyses. However, this does notdistinguish between the collagen types or the location of the cross-link within the molecule. Thefocus in this work was to study the carboxyterminal telopeptide domain of type I collagen for thedifferently 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 differentlycross-linked structures were purified and characterised from human bone by using SP4 togetherwith the earlier developed ICTP assay for trivalently cross-linked C-terminal telopeptide form. Itwas found that the majority of the trivalent cross-links in the C-terminal telopeptide were presentlyunknown structures, other than pyridinoline. A non-cross-linked form of C-terminal telopeptideof á1-chain of type I collagen was also discovered in bone. The epitope of the ICTP assay wascharacterised 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 apeptide detectable by the ICTP assay. Healthy human Achilles tendon comprises mainly of type I collagen. In ruptured Achillestendons, an increased type III collagen content was found. Since the synthesis of type III collagenwas not increased, it is postulated that the type III collagen must have accumulated over a longperiod of time indicative of a long-lasting microtraumatic process in the tendon before the totalrupture occurred. The ICTP content was increased and the ratio of SP4 to ICTP decreased in calcified stenoticaortic valves suggesting a change in the molecular organisation and cross-linking towards the typefound in human bone. The total collagen content was dramatically decreased in the calcifiedvalves. Both in the Achilles tendons and in the aortic valves, the ICTP content was found to decreasewith age with a concomitant increase in the variants of the C-terminal telopeptide structuresdetectable with the SP4 assay, pointing to a change in the molecular organisation of thecollagenous matrix in these tissues.

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