@article{EinarssonBahrkeSigurdssonetal.2013, author = {Einarsson, Jon M. and Bahrke, Sven and Sigurdsson, Bjarni Thor and Ng, Chuen-How and Petersen, Petur Henry and Sigurjonsson, Olafur E. and Jonsson, Halldor and Gislason, Johannes and Thormodsson, Finnbogi R. and Peter, Martin G.}, title = {Partially acetylated chitooligosaccharides bind to YKL-40 and stimulate growth of human osteoarthritic chondrocytes}, series = {Biochemical and biophysical research communications}, volume = {434}, journal = {Biochemical and biophysical research communications}, number = {2}, publisher = {Elsevier}, address = {San Diego}, issn = {0006-291X}, doi = {10.1016/j.bbrc.2013.02.122}, pages = {298 -- 304}, year = {2013}, 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(TM)) and further ultrafiltration produced T-ChOS(TM), 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(TM) and T-ChOS(TM) was determined, revealing 2- to 3-fold increases in cell number. About 500 mu g/ml was needed for Oligomin(TM) and around five times lower concentration for T-ChOS(TM), 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(TM) homologues should resist hydrolysis, point towards a new therapeutic concept for treating inflammatory joint diseases.}, language = {en} }