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The skeletal phenotype of chondroadherin deficient mice.

Hessle, Lovisa LU ; Stordalen, Gunhild A ; Wenglén, Christina LU ; Petzold, Christiane ; Tanner, Elizabeth K ; Brorson, Sverre-Henning ; Baekkevold, Espen S ; Önnerfjord, Patrik LU orcid ; Reinholt, Finn P and Heinegård, Dick LU (2013) In PLoS ONE 8(6).
Abstract
Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3-6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed... (More)
Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3-6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the α1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth. (Less)
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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
6
article number
e63080
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000319872300005
  • pmid:23755099
  • scopus:84878661171
  • pmid:23755099
ISSN
1932-6203
DOI
10.1371/journal.pone.0063080
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151)
id
ba8f4a73-44ad-45e9-a13b-5bec1f7972a9 (old id 3913495)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23755099?dopt=Abstract
date added to LUP
2016-04-01 14:10:34
date last changed
2022-03-29 19:34:40
@article{ba8f4a73-44ad-45e9-a13b-5bec1f7972a9,
  abstract     = {{Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3-6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the α1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth.}},
  author       = {{Hessle, Lovisa and Stordalen, Gunhild A and Wenglén, Christina and Petzold, Christiane and Tanner, Elizabeth K and Brorson, Sverre-Henning and Baekkevold, Espen S and Önnerfjord, Patrik and Reinholt, Finn P and Heinegård, Dick}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{The skeletal phenotype of chondroadherin deficient mice.}},
  url          = {{https://lup.lub.lu.se/search/files/3827672/4091986.pdf}},
  doi          = {{10.1371/journal.pone.0063080}},
  volume       = {{8}},
  year         = {{2013}},
}