title: Effect of NKISK on tendon lengthening: an in vivo model for various clinically applicable dosing regimens.
abstract: One proposed mechanism of tendon lengthening is the "sliding fibril" hypothesis, in which tendons lengthen through the sliding of discontinuous fibrils after release of decorin-fibronectin interfibrillar bonds. The pentapeptide NKISK has been reported to inhibit the binding of decorin, a proteoglycan on the surface of collagen fibrils, to fibronectin, a tissue adhesion molecule, which are thought to play a role in interfibrillar binding. Prior investigations have demonstrated that NKISK produces in vivo tendon lengthening. This study investigates the effect of potential clinically applicable NKISK injection regimens in an in vivo model. One hundred and thirteen male Sprague-Dawley rats were divided into 15 different treatment groups, each receiving percutaneous patellar tendon injections of NKISK, QKTSK (a "nonsense" pentapeptide), or PBS of varying volumes, concentrations, and injection schedules. Following sacrifice, the patellar tendon lengths were measured in all groups, and biomechanical testing was performed with comparisons made to the contralateral, untreated control limbs. Tendon lengthening was significantly greater (p < or = 0.05) in nearly all NKISK-treated tendons as compared to PBS- and QKTSK-treated tendons and was dose-dependent. Measured lengthening was less in rats whose sacrifice was delayed following the final injection of NKISK, which likely indicates recontraction of lengthened tendons, but they remained significantly longer than the controls. Biomechanical testing did not reveal significant differences in ultimate load, modulus, stiffness, or displacement. This study demonstrates that NKISK given in clinically plausible dosing regimens produces dose-dependent tendon lengthening in an in vivo setting with minimal effects on the mechanical properties of the treated tendons.
authors.affiliation: Department of Orthopaedics, Campus Box 7055, Bioinformatics Building, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7055, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Esther
authors.forename: R Alexander
authors.initials: RA
authors.lastname: Creighton
authors.forename: Reid W
authors.initials: RW
authors.lastname: Draeger
authors.forename: Paul S
authors.initials: PS
authors.lastname: Weinhold
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Dahners
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003286:Contracture / Q000188:drug therapy*; D004334:Drug Administration Schedule; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D017847:Patellar Ligament / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C529852:NKISK peptide; D009842:Oligopeptides