Increased C-telopeptide cross-linking of tendon type I collagen in fibromodulin-deficient mice.
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 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.
From the Departments of Clinical Sciences and Sebastian.Kalamajski@med.lu.se.
Sebastian
S
Kalamajski
Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
Cuiping
C
Liu
From the Departments of Clinical Sciences and.
Viveka
V
Tillgren
Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden, the Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden, and.
Kristofer
K
Rubin
Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
Åke
Å
Oldberg
the Department of Orthopædics and Sports Medicine, University of Washington, Seattle, Washington 98195-6500.
Jyoti
J
Rai
the Department of Orthopædics and Sports Medicine, University of Washington, Seattle, Washington 98195-6500.
MaryAnn
M
Weis
the Department of Orthopædics and Sports Medicine, University of Washington, Seattle, Washington 98195-6500.
David R
DR
Eyre
D000447:Aldehydes / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D024042:Collagen Type I / Q000737:chemistry* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency*; D000071235:Fibromodulin; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D011509:Proteoglycans / Q000172:deficiency*; D013710:Tendons / Q000378:metabolism*
D000447:Aldehydes; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D010455:Peptides; D011509:Proteoglycans; C052929:collagen type I trimeric cross-linked peptide; D000071235:Fibromodulin; D008249:Protein-Lysine 6-Oxidase
Collagen; Connective Tissue; Cross-links; Fibromodulin; Lysyl Oxidase; Mass Spectrometry (MS); SLRP; Small Leucine-rich Protein; Tendon