Document Detail

Effect of NKISK on tendon lengthening: an in vivo model for various clinically applicable dosing regimens.
MedLine Citation:
PMID:  18327807     Owner:  NLM     Status:  MEDLINE    
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.
Robert J Esther; R Alexander Creighton; Reid W Draeger; Paul S Weinhold; Laurence E Dahners
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of orthopaedic research : official publication of the Orthopaedic Research Society     Volume:  26     ISSN:  1554-527X     ISO Abbreviation:  J. Orthop. Res.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-18     Completed Date:  2008-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8404726     Medline TA:  J Orthop Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  971-6     Citation Subset:  IM    
Department of Orthopaedics, Campus Box 7055, Bioinformatics Building, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7055, USA.
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MeSH Terms
Contracture / drug therapy*
Drug Administration Schedule
Oligopeptides / administration & dosage*
Patellar Ligament / drug effects*
Rats, Sprague-Dawley
Reg. No./Substance:
0/NKISK peptide; 0/Oligopeptides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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