Sodium cromolyn reduces expression of CTGF, ADAMTS1, and TIMP3 and modulates post-injury patellar tendon morphology

J Orthop Res. 2011 May;29(5):678-83. doi: 10.1002/jor.21291. Epub 2010 Dec 3.

Abstract

The purpose of this study was to determine whether administration of a mast cell inhibitor (sodium cromolyn, SC) would influence tendon repair and extracellular matrix gene expression following acute injury. CD1 mouse patellar tendons were unilaterally injured and mast cell prevalence was determined. The effect of SC injection on tendon hypercellularity, cross-sectional area, collagen organization, and expression of extracellular matrix-related genes was examined. Mast cell prevalence was markedly increased in injured patellar tendons (p = 0.009), especially at 8 weeks post-injury (p = 0.025). SC injection increased collagen organization compared to uninjected animals at 4 weeks and attenuated the development of tendon hypercellularity and tendon thickening post-injury. Expression of CTGF, ADAMTS1, and TIMP3 in injured tendon was reduced in the SC group. SC injections moderated the structural alterations of healing tendon in association with downregulation of several genes associated with tendon fibrosis. This work corroborates previous findings pointing to a role of mast cells in tendon repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / biosynthesis*
  • ADAMTS1 Protein
  • Animals
  • Connective Tissue Growth Factor / biosynthesis*
  • Cromolyn Sodium / pharmacology*
  • Mast Cells / physiology
  • Mice
  • Patellar Ligament / cytology
  • Patellar Ligament / drug effects
  • Patellar Ligament / injuries
  • Patellar Ligament / metabolism*
  • Tissue Inhibitor of Metalloproteinase-3 / biosynthesis*
  • Wound Healing / physiology

Substances

  • CCN2 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-3
  • Connective Tissue Growth Factor
  • ADAM Proteins
  • ADAMTS1 Protein
  • Adamts1 protein, mouse
  • Cromolyn Sodium

Grants and funding