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The role of cartilage glycosaminoglycan structure in gagCEST

Einarsson, Emma LU orcid ; Peterson, Pernilla LU ; Önnerfjord, Patrik LU orcid ; Gottschalk, Michael LU orcid ; Xu, Xiang ; Knutsson, Linda LU orcid ; Dahlberg, Leif E LU ; Struglics, André LU and Svensson, Jonas LU (2020) In NMR in Biomedicine 33(5).
Abstract

Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed... (More)

Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed through the linear regression coefficient with 95% confidence interval of MTRasym per GAG concentration. We observed a lower gagCEST effect in phantoms containing a mixture of CS-A and CS-C compared with phantoms containing mainly CS-A. The difference in response corresponds well to the difference in CS-A concentration. GAG bound in aggrecan from calf articular cartilage, where CS-A is assumed to be the major type of GAG, produed a similar gagCEST effect as that observed for free CS-A. The effect was also similar for aggregated (ie, bound to hyaluronic acid) and nonaggregated aggrecan. In conclusion, our results indicate that the aggrecan structure in itself does not impact the gagCEST effect, but that the effect is strongly dependent on GAG type. In phantoms, the current implementation of gagCEST is sensitive to CS-A while for CS-C, the main GAG component in mature human articular cartilage, the sensitivity is limited. This difference in gagCEST sensitivity between GAG types detected in phantoms is a strong motivation to also explore the possibility of a similar effect in vivo.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NMR in Biomedicine
volume
33
issue
5
article number
e4259
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85078860099
  • pmid:31999387
ISSN
0952-3480
DOI
10.1002/nbm.4259
language
English
LU publication?
yes
id
f9cdea67-6ebe-4d64-af5c-2a9d410743cb
date added to LUP
2020-02-05 08:31:31
date last changed
2024-07-24 13:24:00
@article{f9cdea67-6ebe-4d64-af5c-2a9d410743cb,
  abstract     = {{<p>Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed through the linear regression coefficient with 95% confidence interval of MTRasym per GAG concentration. We observed a lower gagCEST effect in phantoms containing a mixture of CS-A and CS-C compared with phantoms containing mainly CS-A. The difference in response corresponds well to the difference in CS-A concentration. GAG bound in aggrecan from calf articular cartilage, where CS-A is assumed to be the major type of GAG, produed a similar gagCEST effect as that observed for free CS-A. The effect was also similar for aggregated (ie, bound to hyaluronic acid) and nonaggregated aggrecan. In conclusion, our results indicate that the aggrecan structure in itself does not impact the gagCEST effect, but that the effect is strongly dependent on GAG type. In phantoms, the current implementation of gagCEST is sensitive to CS-A while for CS-C, the main GAG component in mature human articular cartilage, the sensitivity is limited. This difference in gagCEST sensitivity between GAG types detected in phantoms is a strong motivation to also explore the possibility of a similar effect in vivo.</p>}},
  author       = {{Einarsson, Emma and Peterson, Pernilla and Önnerfjord, Patrik and Gottschalk, Michael and Xu, Xiang and Knutsson, Linda and Dahlberg, Leif E and Struglics, André and Svensson, Jonas}},
  issn         = {{0952-3480}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{NMR in Biomedicine}},
  title        = {{The role of cartilage glycosaminoglycan structure in gagCEST}},
  url          = {{http://dx.doi.org/10.1002/nbm.4259}},
  doi          = {{10.1002/nbm.4259}},
  volume       = {{33}},
  year         = {{2020}},
}