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Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism

Sara Groeneboer, Stijn Lambrecht UGent, Aad Dhollander, Peggy Jacques UGent, Bert Vandercruyssen, Katrien Devreese UGent, Dirk Elewaut UGent and August Verbruggen UGent (2010) OSTEOARTHRITIS AND CARTILAGE. 18(suppl. 2). p.S107-S108
abstract
Objectives: To compare the ability of different cyclodextrin polysulphate derivatives to affect human articular cartilage cell metabolism in vitro and to act as Disease Modifying OsteoArthritis Drugs in vivo. Methods: OA chondrocytes were cultured in gelled alginate and exposed to 5 µg/ml of 2,3,6-tri-O-methyl-β-cyclodextrin (ME-CD), 2,3-di-O-methyl-6-sulphate-β-cyclodextrin (ME-CD-6-S), 2,6-di-O-methyl-3-sulphate-β-cyclodextrin (ME-CD-3-S), (2-carboxyethyl)-β-cyclodextrin polysulphate (CE-CDPS), (2-hydroxypropyl)-β-cyclodextrin polysulphate (HP-CDPS), 6-monoamino-6-monodeoxy-β-cyclodextrin polysulphate (MA-CDPS) or β-cyclodextrin polysulphate (CDPS) during 5 days. Effects on IL-1-driven chondrocyte extracellular matrix (ECM) metabolism was assayed by analysis of the accumulation of aggrecan in the interterritorial matrix and by the release of IL-6 in the culture supernatant. MA-CDPS, HP-CDPS, CE-CDPS and CDPS were analyzed for their in vitro effect on coagulation and their ability to activate platelets in an in vitro assay to detect possible crossreactivity with HIT (heparin-induced thrombocytopenia) antibodies. CE-CDPS was selected for further qPCR analyses, in order to investigate whether this compound directly influences the gene expression of IL-6 and aggrecan. Results: The monosulphated cyclodextrins ME-CD-6-S and -3S failed to affect aggrecan synthesis and IL-6 secretion by the OA chondrocytes. Polysulphated cyclodextrins MA-CDPS, HP-CDPS, CE-CDPS and CDPS at 5 µg/ml concentrations, on the other hand, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. Five µg/ml of CE-CDPS, in contrast to MA-CDPS, HP-CDPS and CDPS, did not significantly activate platelets and thus showed no potential to induce HIT thromboembolic accidents in vivo. Therefore, CE-CDPS was selected for further qPCR analyses. These analyses confirmed the anabolic and anti-catabolic profile of CE-CDPS. Conclusions: CE-CDPS is a new, structurally adjusted sulphated β-cyclodextrin derivative with preserved chondroprotective capacity and a promising safety profile.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
in
OSTEOARTHRITIS AND CARTILAGE
Osteoarthritis Cartilage
volume
18
issue
suppl. 2
article number
abstract 234
pages
S107 - S108
conference name
2010 World Congress on Osteoarthitis
conference location
Brussels, Belgium
conference start
2010-09-23
conference end
2010-09-26
JCR category
ORTHOPEDICS
JCR impact factor
3.953 (2010)
JCR rank
1/60 (2010)
JCR quartile
1 (2010)
ISSN
1063-4584
DOI
10.1016/S1063-4584(10)60261-0
language
English
UGent publication?
yes
classification
C3
copyright statement
I have transferred the copyright for this publication to the publisher
id
1048629
handle
http://hdl.handle.net/1854/LU-1048629
date created
2010-10-04 10:08:39
date last changed
2016-12-21 15:40:46
@inproceedings{1048629,
  abstract     = {Objectives: To compare the ability of different cyclodextrin polysulphate derivatives to affect human articular cartilage cell metabolism in vitro and to act as Disease Modifying OsteoArthritis Drugs in vivo.
Methods: OA chondrocytes were cultured in gelled alginate and exposed to 5 {\textmu}g/ml of 2,3,6-tri-O-methyl-\ensuremath{\beta}-cyclodextrin (ME-CD), 2,3-di-O-methyl-6-sulphate-\ensuremath{\beta}-cyclodextrin (ME-CD-6-S), 2,6-di-O-methyl-3-sulphate-\ensuremath{\beta}-cyclodextrin (ME-CD-3-S), (2-carboxyethyl)-\ensuremath{\beta}-cyclodextrin polysulphate (CE-CDPS), (2-hydroxypropyl)-\ensuremath{\beta}-cyclodextrin polysulphate (HP-CDPS), 6-monoamino-6-monodeoxy-\ensuremath{\beta}-cyclodextrin polysulphate (MA-CDPS) or \ensuremath{\beta}-cyclodextrin polysulphate (CDPS) during 5 days. Effects on IL-1-driven chondrocyte extracellular matrix (ECM) metabolism was assayed by analysis of the accumulation of aggrecan in the interterritorial matrix and by the release of IL-6 in the culture supernatant. MA-CDPS, HP-CDPS, CE-CDPS and CDPS were analyzed for their in vitro effect on coagulation and their ability to activate platelets in an in vitro assay to detect possible crossreactivity with HIT (heparin-induced thrombocytopenia) antibodies. CE-CDPS was selected for further qPCR analyses, in order to investigate whether this compound directly influences the gene expression of IL-6 and aggrecan.
Results: The monosulphated cyclodextrins ME-CD-6-S and -3S failed to affect aggrecan synthesis and IL-6 secretion by the OA chondrocytes. Polysulphated cyclodextrins MA-CDPS, HP-CDPS, CE-CDPS and CDPS at 5 {\textmu}g/ml concentrations, on the other hand, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. Five {\textmu}g/ml of CE-CDPS, in contrast to MA-CDPS, HP-CDPS and CDPS, did not significantly activate platelets and thus showed no potential to induce HIT thromboembolic accidents in vivo. Therefore, CE-CDPS was selected for further qPCR analyses. These analyses confirmed the anabolic and anti-catabolic profile of CE-CDPS. 
Conclusions: CE-CDPS is a new, structurally adjusted sulphated \ensuremath{\beta}-cyclodextrin derivative with  preserved chondroprotective capacity and a promising safety profile.},
  articleno    = {abstract 234},
  author       = {Groeneboer, Sara and Lambrecht, Stijn and Dhollander, Aad and Jacques, Peggy and Vandercruyssen, Bert and Devreese, Katrien and Elewaut, Dirk and Verbruggen, August},
  booktitle    = {OSTEOARTHRITIS AND CARTILAGE},
  issn         = {1063-4584},
  language     = {eng},
  location     = {Brussels, Belgium},
  number       = {suppl. 2},
  pages        = {abstract 234:S107--abstract 234:S108},
  title        = {Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism},
  url          = {http://dx.doi.org/10.1016/S1063-4584(10)60261-0},
  volume       = {18},
  year         = {2010},
}

Chicago
Groeneboer, Sara, Stijn Lambrecht, Aad Dhollander, Peggy Jacques, Bert Vandercruyssen, Katrien Devreese, Dirk Elewaut, and August Verbruggen. 2010. “Optimized Alkylated Cyclodextrin Polysulphates Restore Osteoarthritic Chondrocyte Extracellular Matrix Metabolism.” In Osteoarthritis and Cartilage, 18:S107–S108.
APA
Groeneboer, S., Lambrecht, S., Dhollander, A., Jacques, P., Vandercruyssen, B., Devreese, K., Elewaut, D., et al. (2010). Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism. OSTEOARTHRITIS AND CARTILAGE (Vol. 18, pp. S107–S108). Presented at the 2010 World Congress on Osteoarthitis.
Vancouver
1.
Groeneboer S, Lambrecht S, Dhollander A, Jacques P, Vandercruyssen B, Devreese K, et al. Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism. OSTEOARTHRITIS AND CARTILAGE. 2010. p. S107–S108.
MLA
Groeneboer, Sara, Stijn Lambrecht, Aad Dhollander, et al. “Optimized Alkylated Cyclodextrin Polysulphates Restore Osteoarthritic Chondrocyte Extracellular Matrix Metabolism.” Osteoarthritis and Cartilage. Vol. 18. 2010. S107–S108. Print.