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Increased C-Telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice.

Kalamajski, Sebastian LU ; Liu, Cuiping LU ; Tillgren, Viveka LU ; Rubin, Kristofer; Oldberg, Åke LU ; Rai, Jyoti; Weis, MaryAnn and Eyre, David R (2014) In Journal of Biological Chemistry 289(27). p.18873-18879
Abstract
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
289
issue
27
pages
18873 - 18879
publisher
ASBMB
external identifiers
  • pmid:24849606
  • wos:000339062900021
  • scopus:84903827555
ISSN
1083-351X
DOI
10.1074/jbc.M114.572941
language
English
LU publication?
yes
id
331be3b1-ded7-42bb-b59c-da337b95779f (old id 4453951)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24849606?dopt=Abstract
date added to LUP
2014-06-04 22:55:47
date last changed
2017-11-05 03:10:21
@article{331be3b1-ded7-42bb-b59c-da337b95779f,
  abstract     = {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.},
  author       = {Kalamajski, Sebastian and Liu, Cuiping and Tillgren, Viveka and Rubin, Kristofer and Oldberg, Åke and Rai, Jyoti and Weis, MaryAnn and Eyre, David R},
  issn         = {1083-351X},
  language     = {eng},
  number       = {27},
  pages        = {18873--18879},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Increased C-Telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice.},
  url          = {http://dx.doi.org/10.1074/jbc.M114.572941},
  volume       = {289},
  year         = {2014},
}