Examining The Effect Of Hyaluronic Acid Receptor Interaction In Healing Tendon
Hyaluronic acid (HA) is a polysaccharide that is present within the extracellular matrix of many connective tissues, including tendon. Recent studies have revealed an active role for HA during wound healing, whereby it induces inflammatory gene expression through direct interaction with cell surface receptors. The specific source and function of HA in wound healing remain poorly defined, however two cell-associated HA receptors, CD44 and Receptor for HA-Mediated Motility (RHAMM) have been shown to mediate many of its biologic effects. CD44 is ubiquitously distributed in tissues and has been implicated in lymphocyte homing, leukocyte activation, and cell adhesion. CD44 also mediates the uptake and clearance of HA. RHAMM has been identified as a critical regulator of cell chemotaxis and, like CD44, has been associated with multiple early inflammatory events. It has not, however, been shown to promote the endocytosis and subsequent delivery of HA for lysosomal digestion, as has CD44.Elucidating the mechanisms by which HA/receptor interaction influences tendon healing and understanding the contribution of the molecules involved may enable us to identify new targets for therapeutic intervention after tendon injury. Therefore, the overall aim of this study is to examine the effect of HA/receptor interaction in healing tendon and to determine the role of key mediators in this process. The overall hypothesis is that HA/receptor interactions, primarily those mediated by its cell associated receptors CD44 and RHAMM, are critical for initiation and regulation of the inflammatory cascade that characterizes adult tendon healing, and for the fibrosis that ensues.