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Nanomechanical phenotype of chondroadherin-null murine articular cartilage.

Batista, Michael A; Nia, Hadi T; Önnerfjord, Patrik LU ; Cox, Karen A; Ortiz, Christine; Grodzinsky, Alan LU ; Heinegård, Dick LU and Han, Lin (2014) In Matrix Biology 38(Jun 2). p.84-90
Abstract
Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈70-80% reduction in the indentation modulus, Eind, of the superficial zone knee cartilage of 11weeks,... (More)
Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈70-80% reduction in the indentation modulus, Eind, of the superficial zone knee cartilage of 11weeks, 4months and 1year old animals. This mechanical phenotype correlates well with observed increases in the heterogeneity collagen fibril diameters in the surface zone. The results suggest that CHAD mainly plays a major role in regulating the formation of the collagen fibrillar network during the early skeletal development. In contrast, CHAD-deletion had no appreciable effects on the indentation mechanics of middle/deep zone cartilage, likely due to the dominating role of aggrecan in the middle/deep zone. The presence of significant rate dependence of the indentation stiffness in both WT and CHAD(-/-) knee cartilage suggested the importance of both fluid flow induced poroelasticity and intrinsic viscoelasticity in murine cartilage biomechanical properties. Furthermore, the marked differences in the nanomechanical behavior of WT versus CHAD(-/-) cartilage contrasted sharply with the relative absence of overt differences in histological appearance. These observations highlight the sensitivity of nanomechanical tools in evaluating structural and mechanical phenotypes in transgenic mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Matrix Biology
volume
38
issue
Jun 2
pages
84 - 90
publisher
Elsevier
external identifiers
  • pmid:24892719
  • wos:000343844500009
  • scopus:84908463601
ISSN
1569-1802
DOI
10.1016/j.matbio.2014.05.008
language
English
LU publication?
yes
id
7ded7cbd-674a-4f13-8842-aa8d1afab596 (old id 4529324)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24892719?dopt=Abstract
date added to LUP
2014-07-04 14:05:25
date last changed
2017-10-01 03:12:25
@article{7ded7cbd-674a-4f13-8842-aa8d1afab596,
  abstract     = {Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈70-80% reduction in the indentation modulus, Eind, of the superficial zone knee cartilage of 11weeks, 4months and 1year old animals. This mechanical phenotype correlates well with observed increases in the heterogeneity collagen fibril diameters in the surface zone. The results suggest that CHAD mainly plays a major role in regulating the formation of the collagen fibrillar network during the early skeletal development. In contrast, CHAD-deletion had no appreciable effects on the indentation mechanics of middle/deep zone cartilage, likely due to the dominating role of aggrecan in the middle/deep zone. The presence of significant rate dependence of the indentation stiffness in both WT and CHAD(-/-) knee cartilage suggested the importance of both fluid flow induced poroelasticity and intrinsic viscoelasticity in murine cartilage biomechanical properties. Furthermore, the marked differences in the nanomechanical behavior of WT versus CHAD(-/-) cartilage contrasted sharply with the relative absence of overt differences in histological appearance. These observations highlight the sensitivity of nanomechanical tools in evaluating structural and mechanical phenotypes in transgenic mice.},
  author       = {Batista, Michael A and Nia, Hadi T and Önnerfjord, Patrik and Cox, Karen A and Ortiz, Christine and Grodzinsky, Alan and Heinegård, Dick and Han, Lin},
  issn         = {1569-1802},
  language     = {eng},
  number       = {Jun 2},
  pages        = {84--90},
  publisher    = {Elsevier},
  series       = {Matrix Biology},
  title        = {Nanomechanical phenotype of chondroadherin-null murine articular cartilage.},
  url          = {http://dx.doi.org/10.1016/j.matbio.2014.05.008},
  volume       = {38},
  year         = {2014},
}