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Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism

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Abstract
Purpose: 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 and Materials: OA chondrocytes were cultured in gelled alginate and exposed to 5 μg/ml (2-carboxyethyl)-β-cyclodextrin polysulphate (CE-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. The compounds 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. The effectiveness of CE-CDPS was further assayed in collagenase-induced OA of the knee, by injecting 1 mg/kg CE-CDPS or saline subcutaneously once weekly in a mouse model. Knee joints were scored semiquantitatively on inflammation, fibrosis, osteophyte growth and loss of articular cartilage and Safranin-O staining. Results: The polysulphated cyclodextrin CE-CDPS at 5 μg/ml concentrations, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. Five μg/ml of CE-CDPS, in contrast to other polysulphated cyclodextrins, 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. CE-CDPS was therefore tested on collagenase–induced knee OA in mice and was shown to prevent cartilage proteoglycan depletion but not osteophyte formation in the OA knee joints of these mice. Conclusions: CE-CDPS is a new, structurally adjusted sulphated β-cyclodextrin derivative with preserved chondroprotective capacity and a promising safety profile.

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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 International Cartilage Repair Society, 9th World Congress, Abstracts.
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. International Cartilage Repair Society, 9th World congress, Abstracts. Presented at the 9th World congress of the International Cartilage Repair Society (ICRS 2010).
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. International Cartilage Repair Society, 9th World congress, Abstracts. 2010.
MLA
Groeneboer, Sara, Stijn Lambrecht, Aad Dhollander, et al. “Optimized Alkylated Cyclodextrin Polysulphates Restore Osteoarthritic Chondrocyte Extracellular Matrix Metabolism.” International Cartilage Repair Society, 9th World Congress, Abstracts. 2010. Print.
@inproceedings{1048644,
  abstract     = {Purpose: 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 and Materials: OA chondrocytes were cultured in gelled alginate and exposed to 5 \ensuremath{\mu}g/ml (2-carboxyethyl)-\ensuremath{\beta}-cyclodextrin polysulphate (CE-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. The compounds 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. The effectiveness of CE-CDPS was further assayed in collagenase-induced OA of the knee, by injecting 1 mg/kg CE-CDPS or saline subcutaneously once weekly in a mouse model. Knee joints were scored semiquantitatively on inflammation, fibrosis, osteophyte growth and loss of articular cartilage and Safranin-O staining.
Results: The polysulphated cyclodextrin CE-CDPS at 5 \ensuremath{\mu}g/ml concentrations, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. Five \ensuremath{\mu}g/ml of CE-CDPS, in contrast to other polysulphated cyclodextrins, 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. CE-CDPS was therefore tested on collagenase--induced knee OA in mice and was shown to prevent cartilage proteoglycan depletion but not osteophyte formation in the OA knee joints of these mice.
Conclusions: CE-CDPS is a new, structurally adjusted sulphated \ensuremath{\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 Vandercruyssen, Bert and Devreese, Katrien and Elewaut, Dirk and Verbruggen, August},
  booktitle    = {International Cartilage Repair Society, 9th World congress, Abstracts},
  language     = {eng},
  location     = {Sitges, Spain},
  title        = {Optimized alkylated cyclodextrin polysulphates restore osteoarthritic chondrocyte extracellular matrix metabolism},
  year         = {2010},
}