title: Low-Dose and Short-Duration Matrix Metalloproteinase 9 Inhibition Does Not Affect Adhesion Formation during Murine Flexor Tendon Healing.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Orner
authors.forename: Michael B
authors.initials: MB
authors.lastname: Geary
authors.forename: Warren C
authors.initials: WC
authors.lastname: Hammert
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Alayna E
authors.initials: AE
authors.lastname: Loiselle
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012016:Reference Values; D013708:Tendon Injuries / Q000188:drug therapy / Q000601:surgery*; D013718:Tensile Strength / Q000187:drug effects; D000267:Tissue Adhesions / Q000188:drug therapy / Q000201:enzymology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; C106997:Ro 32-3555; D020780:Matrix Metalloproteinase 9