The polysaccharide hyaluronan (HA) is produced by cell membrane-embedded synthase enzymes and can be bound to cell surface receptors to anchor the pericellular matrix. HA interactions with proteoglycans and other HA-binding proteins lead to a highly hydrated protective network. HA contributes to a defensive response to inflammation and microbial attack. We will document and explain the correlation between increased HA synthesis and defense against reactive oxygen and nitrogen species (ROS/RNS) or other inflammation mediators. Increased HA content also alters the osmotic and viscoelastic properties of the matrix, driving the formation and controlling the transport of extracellular vesicles mediating cell-cell communication. We also show how excessive degradation of HA by ROS/RNS leads to fragmentation and altered cell signaling by de-clustering of cell surface receptors. We tested the concept of using a specific HA-binding peptide to modulate the interaction of HA or its fragments with its CD44 receptors and co-receptors such as Toll-like receptors and RHAMM, in a model for cartilage repair. A 15mer HA-binding peptide, coupled with microfracture as a source of bone marrow derived mesenchymal stem cells, was found to show promise for non-fibrotic repair of a full thickness defect in articular cartilage.
Mary K. Cowman, Ph.D., received her Ph.D. in Chemistry from Case Western Reserve University. She completed postdoctoral training in Biochemistry at Brandeis University, and in Ophthalmology Research at Columbia University College of Physicians and Surgeons. She is Professor of Biomedical Engineering in the NYU Tandon School of Engineering, and Professor of Orthopaedic Surgery in the NYU Grossman School of Medicine. Dr. Cowman’s research concerns discovery and development of new biotherapeutics, biomarkers, and bioactive materials based on cellular response to components of the extracellular matrix, with special expertise in hyaluronan polysaccharide.