title: The effect of NKISK on tendon in an in vivo model.
abstract: The mechanism through which ligaments and tendons change length during growth and contracture is unclear. It has been hypothesized that there is a reversible "interfibrillar bond" that, when broken, allows the sliding of collagen fibrils past one another during length changes. The pentapeptide NKISK has been reported to inhibit the binding of decorin to fibronectin. This study was designed to evaluate the effect of NKISK in an in vivo model. Male Sprague-Dawley rats were divided into three groups (n = 9, 9 and 14, respectively). The left patellar tendon was injected with 1.0 ml of NKISK (Group 1 = 1.0 mM, Groups 2 and 3 = 5.0 mM). The contralateral/control limb was injected with carrier. Group 1 was sacrificed after three, Group 2 after four and Group 3 after seven daily injections. The patellar tendon lengths were measured in all groups with comparisons made to the contralateral control limb. NKISK injection resulted in a significant increase in length in Group 2 (3.14% +/- 2.04, P = 0.002) and in Group 3 (6.12% +/- 3.84, P < 0.001). Biomechanical testing of Group 3 showed no differences in maximum load, ultimate strength, structural stiffness, or elastic modulus of the treated tendons but did demonstrate a statistically significant decrease in the displacement and strain at maximum load in the NKISK-treated tendons. This study demonstrates that inhibition of decorin/fibronectin binding by NKISK results in tendon lengthening in an in vivo setting as noted by a progressive increase in the length of the patellar tendon.
authors.affiliation: Deportment of Orthopedic Surgery, University of North Carolina School of Medicine, Chapel Hill 27599-7055, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Caprise
authors.forename: G E
authors.initials: GE
authors.lastname: Lester
authors.forename: P
authors.initials: P
authors.lastname: Weinhold
authors.forename: J
authors.initials: J
authors.lastname: Hill
authors.forename: L E
authors.initials: LE
authors.lastname: Dahners
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins / Q000378:metabolism; D007719:Knee Joint / Q000502:physiology; D008297:Male; D023421:Models, Animal; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013710:Tendons / Q000187:drug effects* / Q000502:physiology*
chemical_list: D058575:Decorin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D010446:Peptide Fragments; D011509:Proteoglycans