Advanced search
1 file | 250.70 KB

Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism

(2010) OSTEOARTHRITIS AND CARTILAGE. 18(suppl. 2). p.S107-S108
Author
Organization
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.

Downloads

    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 250.70 KB

Citation

Please use this url to cite or link to this publication:

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.
@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},
}

Altmetric
View in Altmetric