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Increased C-telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2014 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, no 27, 18873-18879 p.Article in journal (Refereed) Published
Abstract [en]

The controlled assembly of collagen monomers into fibrils, with accompanying intermolecular cross-linking by lysyl oxidase-mediated bonds, is vital to the structural and mechanical integrity of connective tissues. This process is influenced by collagen-associated proteins, including small leucine-rich proteins (SLRPs), but the regulatory mechanisms are not well understood. Deficiency in fibromodulin, an SLRP, causes abnormal collagen fibril ultrastructure and decreased mechanical strength in mouse tendons. In this study, fibromodulin deficiency rendered tendon collagen more resistant to nonproteolytic extraction. The collagen had an increased and altered cross-linking pattern at an early stage of fibril formation. Collagen extracts contained a higher proportion of stably crosslinked alpha 1(I) chains as a result of their C-telopeptide lysines being more completely oxidized to aldehydes. The findings suggest that fibromodulin selectively affects the extent and pattern of lysyl oxidase-mediated collagen cross-linking by sterically hindering access of the enzyme to telopeptides, presumably through binding to the collagen. Such activity implies a broader role for SLRP family members

Place, publisher, year, edition, pages
2014. Vol. 289, no 27, 18873-18879 p.
National Category
Basic Medicine
URN: urn:nbn:se:uu:diva-230094DOI: 10.1074/jbc.M114.572941ISI: 000339062900021OAI: oai:DiVA.org:uu-230094DiVA: diva2:742847
Available from: 2014-09-02 Created: 2014-08-19 Last updated: 2014-09-02Bibliographically approved

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Rubin, Kristofer
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Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLab
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