Hyaluronic acid (HA) is a polysaccharide that is present within the extracellular matrix (ECM) of manyconnective tissues, including tendon. Recent studies have revealed an active role for HA during woundhealing, whereby it induces inflammatory gene expression through direct interaction with cell surfacereceptors. The overall aim of this bioengineering study is to examine the effect of HA/receptor interaction inhealing tendon and to determine the role of key mediators in this process. The overall hypothesis is thatHA/receptor interactions, primarily those mediated by its cell associated receptors CD44 and RHAMM, arecritical for initiation and regulation of the inflammatory cascade that characterizes adult tendon healing, andfor the fibrosis that ensues.
Our specific aims and hypotheses are:
Specific Aim 1 : To analyze the effects ofglobally inhibiting HA/receptor interactions in injured patellar tendons by evaluating the inflammatory cytokineresponse and mechanical properties of the injured tissue. Hypothesis 1A: Tendons of mice treated with apeptide that competitively inhibits HA/receptor interactions will exhibit decreased expression of proinflammatorycytokines one and three days post-injury. Hypothesis 1B: Tendons of mice treated with apeptide that competitively inhibits HA/receptor interactions will exhibit superior mechanical properties threeand six weeks post-injury.
Specific Aim 2 : To analyze the effects of CD44 deficiency in injured patellartendons by evaluating the inflammatory cytokine response and mechanical properties of the injured tissue.Hypothesis 2A: Tendons of CD44 knockout mice will exhibit decreased expression of pro-inflammatorycytokines one and three days post-injury. Hypothesis 2B: Tendons of CD44 knockout mice will exhibitinferior mechanical properties three and six weeks post-injury.
Specific Aim 3 : To analyze the effects ofRHAMM deficiency in injured patellar tendons by evaluating the inflammatory cytokine response andmechanical properties of the injured tissue. Hypothesis 3A: Tendons of RHAMM knockout mice will exhibitdecreased expression of pro-inflammatory cytokines one and three days post-injury. Hypothesis 3B:Tendons of RHAMM knockout mice will exhibit superior mechanical properties three and six weeks postinjury.Although a great deal of insight has been gained into HA and its receptors with regard to their roles ininflammation, little is known about their involvement in tendon healing. If successful, this study will betterdefine the functions of two important HA receptors and help to determine the effect of HA/receptor interactionon tendon wound healing. This information will present exciting avenues for the development of novel,clinical applications and thus lead to immensely beneficial improvements in the treatment of tendon injuries.
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