Partially acetylated chitooligosaccharides bind to YKL-40 and stimulate growth of human osteoarthritic chondrocytes

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• 作者：Jon M. Einarsson^a ; ^jon@genis.is ; Sven Bahrke^b ; Bjarni Thor Sigurdsson^c ; Chuen-How Ng^a ; Petur Henry Petersen^c ; Olafur E. Sigurjonsson^d ; ^f ; Halldor Jonsson Jr.^e ; Johannes Gislason^a ; Finnbogi R. Thormodsson^c ; ^g ; Martin G. Peter^b
• 关键词：Cell culture ; Chitolectin ; Chitooligosaccharides ; Chondrocytes ; High affinity binding ; Rheumatoid arthritis ; YKL-40
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：3 May, 2013
• 年：2013
• 卷：434
• 期：2
• 页码：298-304
• 全文大小：834 K

文摘

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 ¦Ìg/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.