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

(2011) RHEUMATOLOGY. 50(7). p.1226-1235
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
Chondroprotection, Cyclodextrin polysulphates., Osteoarthritis

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Citation

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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.
@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},
}

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