The Johns Hopkins University

Jeannine Coburn

Jennifer H Elisseeff

Kevin J Yarema

Udayanath Aich

A new class of molecules, C&#x2014;OH tributanoylated hexosamines, including, for example, GalNAc, GlcNAc and ManNAc, are demonstrated to increase cartilage-like tissue accumulation by IL-1&#x3b2;-stimulated chondrocytes. Furthermore, all three molecules reduced NFKB1 and I&#x3ba;B&#x3b1; driven gene expression, consistent with NF&#x3ba;B inhibitory properties of these analogs. GalNAc-a exposure produced the greatest ECM accumulation by IL-1&#x3b2;-stimulated chondrocytes. However, GalNAc-a exposure produced an opposite effect on MSC exposure, where a decrease in ECM accumulation was observed. These findings are in support of the function of NF&#x3ba;B signaling during limb development and growth plate chondrogenesis. The present invention shows the capability of this new class of hexosamine analogs as disease-modifying agents for treating cartilage damage.

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Baltimore, MD, United States of America

Jeannine Coburn