Increased C-Telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice.
Author
Summary, in English
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 non-proteolytic 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 cross-linked α1(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 in regulating collagen cross-linking placement and quantity.
Department/s
- Åke Oldberg´s group
- Rheumatology
- Department of Experimental Medical Science
Publishing year
2014
Language
English
Pages
18873-18879
Publication/Series
Journal of Biological Chemistry
Volume
289
Issue
27
Full text
Links
Document type
Journal article
Publisher
American Society for Biochemistry and Molecular Biology
Topic
- Cell and Molecular Biology
Status
Published
Research group
- Åke Oldberg´s group
ISBN/ISSN/Other
- ISSN: 1083-351X