Title

Enhancement of Achilles Tendon Repair Mediated by Matrix Metalloproteinase Inhibition via Systemic Administration of Doxycycline

Publication Date

2014

Journal Title

J Orthop Res

Abstract

Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP-8 activity from 2 to 6 weeks post-injury, with peak increases in activity occurring at 4 weeks post-injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP-8 activity in situ. Our findings suggest that inhibition of MMP-8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:500-506, 2014.

Volume Number

32

Issue Number

4

Pages

500-506

Document Type

Article

EPub Date

2013/12/19

Status

Faculty; Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

Orthopedic Surgery; Neurosurgery

PMID

24346815

DOI

10.1002/jor.22564

Comments

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