Paper 2: An In Vivo Application of Interleukin-1 Receptor Antagonist Inhibits Deterioration of Mechanical Properties of the Stress-shielded Patellar Tendon Without Significant Changes in the Fascicle Properties

Abstract

IntroductionDisuse of diarthrodial joints is accompanied not only by many musculoskeletal problems, but also as an adverse outcome of treatments for various disorders, such as immobilization. Stress deprivation has been regarded as the most essential causative factor in joint disuse [1Amiel et al.Connect Tissue Res. 1980; Google Scholar]. In a series of our previous studies [2Yamamoto et al.JBE. 1993; Google Scholar, 3Majima et al.JOR. 1996; Google Scholar], we have developed a stress-shielding model for the patellar tendon without joint immobilization and demonstrated that stress deprivation dramatically deteriorates the mechanical properties of the rabbit patellar tendon, depending on the degree of shielded stress. However, the mechanism of the tendon deterioration caused by stress deprivation has not been clarified as of yet. Recently, the authors have found that interleukin (IL)-1-beta is over-expressed in the fibroblasts of the stress-shielded patellar tendon using the stress-shielding model [4Uchida et al.JB. 2005; Google Scholar]. It is known that IL-1-beta induces matrix metallo-proteinases (MMPs)-1, -3, and -13 in tendon fibroblasts [5Tsuzaki et al.JOR. 2003; Google Scholar] and that IL-1beta inhibits collagen synthesis in tendon fibroblasts [6Bhatnagar et al.Biochem Int. 1986; Google Scholar]. Therefore, there is a possibility that IL-1-beta plays a role in the tendon deterioration in response to stress deprivation. Then, we have conducted a study in which the IL-1 functions are inhibited with IL-1 receptor antagonist (IL-1ra) in the stress-shielding model. We have hypothesized that a local administration of IL-1-ra may inhibit the deterioration of the stress-shielded patellar tendon. On the other hand, the tendon tissues have a hierarchical structure composed of bundles, fascicles, fibrils and fibers [7Kastelic et al.Connect Tissue Res. 1978; PubMed Google Scholar]. Yamamoto et al [8Yamamoto et al.Clin Biomech. 1999; PubMed Google Scholar] found that the effect of stress shielding on the mechanical properties of patellar tendon fascicles is much smaller than that of bulk tendons. They suggested that the stress shielding predominantly affects mechanical interaction among collagen fascicles or among collagen fascicles and other minor matrix proteins in the patellar tendon rather than affects the mechanical properties of collagen fascicles themselves. Therefore, we have made the second hypothesis that the effect of the IL-1-ra application on mechanical properties of the fascicles harvested from the stress-shielded patellar tendon may not be significant. The purpose of this study is to test these two hypotheses.