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Optimized alkylated cyclodextrin polysulphates with reduced risks on thromboembolic accidents improve osteoarthritic chondrocyte metabolism

Sara Groeneboer UGent, Stijn Lambrecht UGent, AAD DHOLLANDER UGent, PEGGY JACQUES UGent, BERT VANDER CRUYSSEN UGent, Rik J Lories, Katrien Devreese UGent, Koen Chiers UGent, Dirk Elewaut UGent and August Verbruggen UGent (2011) RHEUMATOLOGY. 50(7). p.1226-1235
abstract
Methods. OA chondrocytes were cultured in alginate and exposed to 5 mu g/ml of 2,3,6-tri-O-methyl-beta-cyclodextrin (ME-CD), 2,3-di-O-methyl-6-sulphate-beta-cyclodextrin (ME-CD-6-S), 2,6-di-O-methyl-3-sulphate-beta-cyclodextrin (ME-CD-3-S), (2-carboxyethyl)-beta-CDPS (CE-CDPS), (2-hydroxypropyl)-beta-CDPS (HP-CDPS), 6-monoamino-6-monodeoxy-beta-CDPS (MA-CDPS) or beta-CDPS for 5 days. Effects on IL-1-driven chondrocyte extracellular matrix (ECM) metabolism were assayed by analysis of the accumulation of aggrecan in the interterritorial matrix, IL-6 secretion and qPCR. MA-CDPS, HP-CDPS, CE-CDPS and CDPS were analysed for their in vitro effect on coagulation and their ability to activate platelets in an in vitro assay to detect possible cross-reactivity with heparin-induced thrombocytopenia (HIT) antibodies. Results. The monosulphated cyclodextrins ME-CD-6-S and -3-S 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 mu g/ml concentrations, on the other hand, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. aPTT and PT for all derivatives were lengthened for polysaccharide concentrations > 50 mu g/ml. Five micrograms per millilitre of beta-CDPS concentrations that significantly modulated ECM ground substance production in vitro did not affect aPTT or PT. Furthermore, CE-CDPS, in contrast to MA-CDPS, HP-CDPS and CDPS, did not significantly activate platelets, suggesting a minimal potential to induce HIT thromboembolic accidents in vivo. Conclusions. CE-CDPS is a new, structurally adjusted, sulphated beta-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
journalArticle (original)
publication status
published
subject
keyword
Chondroprotection, Cyclodextrin polysulphates., Osteoarthritis
journal title
RHEUMATOLOGY
Rheumatology
volume
50
issue
7
pages
1226 - 1235
Web of Science type
Article
Web of Science id
000291746100010
JCR category
RHEUMATOLOGY
JCR impact factor
4.058 (2011)
JCR rank
9/29 (2011)
JCR quartile
2 (2011)
ISSN
1462-0324
DOI
10.1093/rheumatology/keq396
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1233839
handle
http://hdl.handle.net/1854/LU-1233839
date created
2011-05-24 14:20:35
date last changed
2013-02-27 09:09:22
@article{1233839,
  abstract     = {Methods. OA chondrocytes were cultured in alginate and exposed to 5 mu g/ml of 2,3,6-tri-O-methyl-beta-cyclodextrin (ME-CD), 2,3-di-O-methyl-6-sulphate-beta-cyclodextrin (ME-CD-6-S), 2,6-di-O-methyl-3-sulphate-beta-cyclodextrin (ME-CD-3-S), (2-carboxyethyl)-beta-CDPS (CE-CDPS), (2-hydroxypropyl)-beta-CDPS (HP-CDPS), 6-monoamino-6-monodeoxy-beta-CDPS (MA-CDPS) or beta-CDPS for 5 days. Effects on IL-1-driven chondrocyte extracellular matrix (ECM) metabolism were assayed by analysis of the accumulation of aggrecan in the interterritorial matrix, IL-6 secretion and qPCR. MA-CDPS, HP-CDPS, CE-CDPS and CDPS were analysed for their in vitro effect on coagulation and their ability to activate platelets in an in vitro assay to detect possible cross-reactivity with heparin-induced thrombocytopenia (HIT) antibodies. 
Results. The monosulphated cyclodextrins ME-CD-6-S and -3-S 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 mu g/ml concentrations, on the other hand, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. aPTT and PT for all derivatives were lengthened for polysaccharide concentrations {\textrangle} 50 mu g/ml. Five micrograms per millilitre of beta-CDPS concentrations that significantly modulated ECM ground substance production in vitro did not affect aPTT or PT. Furthermore, CE-CDPS, in contrast to MA-CDPS, HP-CDPS and CDPS, did not significantly activate platelets, suggesting a minimal potential to induce HIT thromboembolic accidents in vivo. 
Conclusions. CE-CDPS is a new, structurally adjusted, sulphated beta-cyclodextrin derivative with preserved chondroprotective capacity and a promising safety profile.},
  author       = {Groeneboer, Sara and Lambrecht, Stijn and DHOLLANDER, AAD and JACQUES, PEGGY and VANDER CRUYSSEN, BERT and Lories, Rik J and Devreese, Katrien and Chiers, Koen and Elewaut, Dirk and Verbruggen, August},
  issn         = {1462-0324},
  journal      = {RHEUMATOLOGY},
  keyword      = {Chondroprotection,Cyclodextrin polysulphates.,Osteoarthritis},
  language     = {eng},
  number       = {7},
  pages        = {1226--1235},
  title        = {Optimized alkylated cyclodextrin polysulphates with reduced risks on thromboembolic accidents improve osteoarthritic chondrocyte metabolism},
  url          = {http://dx.doi.org/10.1093/rheumatology/keq396},
  volume       = {50},
  year         = {2011},
}

Chicago
Groeneboer, Sara, Stijn Lambrecht, AAD DHOLLANDER, Peggy Jacques, BERT VANDER CRUYSSEN, Rik J Lories, Katrien Devreese, Koen Chiers, Dirk Elewaut, and August Verbruggen. 2011. “Optimized Alkylated Cyclodextrin Polysulphates with Reduced Risks on Thromboembolic Accidents Improve Osteoarthritic Chondrocyte Metabolism.” Rheumatology 50 (7): 1226–1235.
APA
Groeneboer, S., Lambrecht, S., DHOLLANDER, A., Jacques, P., VANDER CRUYSSEN, B., Lories, R. J., Devreese, K., et al. (2011). Optimized alkylated cyclodextrin polysulphates with reduced risks on thromboembolic accidents improve osteoarthritic chondrocyte metabolism. RHEUMATOLOGY, 50(7), 1226–1235.
Vancouver
1.
Groeneboer S, Lambrecht S, DHOLLANDER A, Jacques P, VANDER CRUYSSEN B, Lories RJ, et al. Optimized alkylated cyclodextrin polysulphates with reduced risks on thromboembolic accidents improve osteoarthritic chondrocyte metabolism. RHEUMATOLOGY. 2011;50(7):1226–35.
MLA
Groeneboer, Sara, Stijn Lambrecht, AAD DHOLLANDER, et al. “Optimized Alkylated Cyclodextrin Polysulphates with Reduced Risks on Thromboembolic Accidents Improve Osteoarthritic Chondrocyte Metabolism.” RHEUMATOLOGY 50.7 (2011): 1226–1235. Print.