Caitlin A Orner1, Michael B Geary, Warren C Hammert, Regis J O'Keefe, Alayna E Loiselle. 1. Rochester, N.Y.; and St. Louis, Mo. From the Center for Musculoskeletal Research and Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center; the University of Rochester School of Medicine and Dentistry; and the Department of Orthopaedic Surgery, Washington University School of Medicine.
Abstract
BACKGROUND: After flexor tendon injury and repair, adhesion formation is a substantial concern, as it can result in loss of motion and functional disability. Matrix metalloproteinase 9 (Mmp9) is a gelatinase that contributes to degradation of extracellular matrix and is expressed during flexor tendon healing. Mmp9(-/-) mice have accelerated remodeling of adhesions during flexor tendon healing, relative to wild-type mice. The purpose of this study was to investigate whether Ro 32-3555, an Mmp9 inhibitor, can improve flexor tendon healing by limiting adhesion formation or enhancing remodeling of scar tissue during murine flexor tendon healing. METHODS: Flexor digitorum longus laceration and repair was performed in female C57BL/6J mice. Mice were treated with vehicle or the Mmp9 inhibitor Ro 32-3555 for 8 days. Analysis was performed for digit range of motion and gliding function, biomechanics, gene expression, and Mmp9 activity. RESULTS: An Mmp9 activity assay and zymography confirmed suppression of Mmp9 activity in mice treated with Ro 32-3555. There was no significant difference in tendon gliding or range of motion between vehicle and Ro 32-3555-treated mice. There was also no difference in tendon biomechanical properties between the two groups. CONCLUSION: Local inhibition of Mmp9 gelatinolytic activity at the flexor tendon repair site is insufficient to alter adhesion formation, remodeling of adhesions, or mechanical properties of healing murine flexor tendons.
BACKGROUND: After flexor tendon injury and repair, adhesion formation is a substantial concern, as it can result in loss of motion and functional disability. Matrix metalloproteinase 9 (Mmp9) is a gelatinase that contributes to degradation of extracellular matrix and is expressed during flexor tendon healing. Mmp9(-/-) mice have accelerated remodeling of adhesions during flexor tendon healing, relative to wild-type mice. The purpose of this study was to investigate whether Ro 32-3555, an Mmp9 inhibitor, can improve flexor tendon healing by limiting adhesion formation or enhancing remodeling of scar tissue during murine flexor tendon healing. METHODS: Flexor digitorum longus laceration and repair was performed in female C57BL/6J mice. Mice were treated with vehicle or the Mmp9 inhibitor Ro 32-3555 for 8 days. Analysis was performed for digit range of motion and gliding function, biomechanics, gene expression, and Mmp9 activity. RESULTS: An Mmp9 activity assay and zymography confirmed suppression of Mmp9 activity in mice treated with Ro 32-3555. There was no significant difference in tendon gliding or range of motion between vehicle and Ro 32-3555-treated mice. There was also no difference in tendon biomechanical properties between the two groups. CONCLUSION: Local inhibition of Mmp9 gelatinolytic activity at the flexor tendon repair site is insufficient to alter adhesion formation, remodeling of adhesions, or mechanical properties of healing murine flexor tendons.
Authors: Christopher J Dy; Aaron Daluiski; Huong T Do; Alexia Hernandez-Soria; Robert Marx; Stephen Lyman Journal: J Hand Surg Am Date: 2012-03-28 Impact factor: 2.230
Authors: Graham P Riley; Valerie Curry; Jeroen DeGroot; Benno van El; Nicole Verzijl; Brian L Hazleman; Ruud A Bank Journal: Matrix Biol Date: 2002-03 Impact factor: 11.583
Authors: María Agustina Racca; Pablo Antonio Novoa; Iván Rodríguez; Ana Belén Della Vedova; Claudia Gabriela Pellizas; Marcela Demarchi; Ana Carolina Donadio Journal: Transpl Int Date: 2014-10-02 Impact factor: 3.782
Authors: Derek C Marshall; Susan K Lyman; Scott McCauley; Maria Kovalenko; Rhyannon Spangler; Chian Liu; Michael Lee; Christopher O'Sullivan; Vivian Barry-Hamilton; Haben Ghermazien; Amanda Mikels-Vigdal; Carlos A Garcia; Brett Jorgensen; Arleene C Velayo; Ruth Wang; Joanne I Adamkewicz; Victoria Smith Journal: PLoS One Date: 2015-05-11 Impact factor: 3.240
Authors: Alayna E Loiselle; Benjamin J Frisch; Matthew Wolenski; Justin A Jacobson; Laura M Calvi; Edward M Schwarz; Hani A Awad; Regis J O'Keefe Journal: PLoS One Date: 2012-07-11 Impact factor: 3.240