Partially acetylated chitooligosaccharides bind to YKL-40 and stimulate growth of human osteoarthritic chondrocytes
| Autor: | Pétur Henry Petersen, Chuen-How Ng, Martin G. Peter, Jon M. Einarsson, Johannes Gislason, Olafur E. Sigurjonsson, Halldór Jónsson, Finnbogi R. Thormodsson, Bjarni Sigurdsson, Sven Bahrke |
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| Rok vydání: | 2013 |
| Předmět: |
Cell Survival
Primary Cell Culture Biophysics Oligosaccharides Cell Count Chitin Plasma protein binding Biochemistry Acetylglucosamine Polymerization chemistry.chemical_compound Chondrocytes Adipokines Lectins Osteoarthritis Humans Secretion Chitinase-3-Like Protein 1 Collagen Type II Molecular Biology Cells Cultured biology Chemistry Acetylation Cell Biology Culture Media Ultrafiltration (renal) Cell culture Chitinase Chromatography Gel biology.protein Trisaccharides Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 434:298-304 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2013.02.122 |
| Popis: | Recent evidences indicating that cellular kinase signaling cascades are triggered by oligomers of N-acetylglucosamine (ChOS) and that condrocytes of human osteoarthritic cartilage secrete the inflammation associated chitolectin YKL-40, prompted us to study the binding affinity of partially acetylated ChOS to YKL-40 and their effect on primary chondrocytes in culture. Extensive chitinase digestion and filtration of partially deacetylated chitin yielded a mixture of ChOS (Oligomin™) and further ultrafiltration produced T-ChOS™, with substantially smaller fraction of the smallest sugars. YKL-40 binding affinity was determined for the different sized homologues, revealing micromolar affinities of the larger homologues to YKL-40. The response of osteoarthritic chondrocytes to Oligomin™ and T-ChOS™ was determined, revealing 2- to 3-fold increases in cell number. About 500 μg/ml was needed for Oligomin™ and around five times lower concentration for T-ChOS™, higher concentrations abolished this effect for both products. Addition of chitotriose inhibited cellular responses mediated by larger oligosaccharides. These results, and the fact that the partially acetylated T-ChOS™ homologues should resist hydrolysis, point towards a new therapeutic concept for treating inflammatory joint diseases. |
| Databáze: | OpenAIRE |
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