title: Partially acetylated chitooligosaccharides bind to YKL-40 and stimulate growth of human osteoarthritic chondrocytes.
abstract: 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.
authors.affiliation: Genis hf, KÍM Medical Park, Vatnagarðar 18, IS-104 Reykjavik, Iceland. jon@genis.is
authors.forename: Jon M
authors.initials: JM
authors.lastname: Einarsson
authors.forename: Sven
authors.initials: S
authors.lastname: Bahrke
authors.forename: Bjarni Thor
authors.initials: BT
authors.lastname: Sigurdsson
authors.forename: Chuen-How
authors.initials: CH
authors.lastname: Ng
authors.forename: Petur Henry
authors.initials: PH
authors.lastname: Petersen
authors.forename: Olafur E
authors.initials: OE
authors.lastname: Sigurjonsson
authors.forename: Halldor
authors.initials: H
authors.lastname: Jonsson
authors.forename: Johannes
authors.initials: J
authors.lastname: Gislason
authors.forename: Finnbogi R
authors.initials: FR
authors.lastname: Thormodsson
authors.forename: Martin G
authors.initials: MG
authors.lastname: Peter
mesh_terms: D000107:Acetylation; D000117:Acetylglucosamine / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D002686:Chitin / Q000378:metabolism*; D000071451:Chitinase-3-Like Protein 1; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002850:Chromatography, Gel; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009844:Oligosaccharides / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D058105:Polymerization; D061251:Primary Cell Culture; D011485:Protein Binding; D014312:Trisaccharides / Q000235:genetics / Q000378:metabolism
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D024043:Collagen Type II; D003470:Culture Media; D037102:Lectins; D009844:Oligosaccharides; D014312:Trisaccharides; D002686:Chitin; C041161:chitotriose; D000117:Acetylglucosamine