MMP9 deficiency increased the size of experimentally induced apical periodontitis

J Endod. 2014 May;40(5):658-64. doi: 10.1016/j.joen.2014.01.003. Epub 2014 Mar 18.

Abstract

Introduction: Apical periodontitis is an inflammation and destruction of periapical tissues. Matrix metalloproteinase-9 (MMP-9) is thought to be involved in periapical lesion formation and progression. The aim of this study was to evaluate the lesion progression in MMP-9 knockout (KO) mice compared with that in control mice (wild type [WT]).

Methods: The pulps of mouse mandibular first molars were exposed; animals were killed at 0, 7, 14, 21, and 28 days after surgery. Hematoxylin-eosin-stained sections were observed for the description of pulpal, apical, periapical features, and the periapical lesion size. The periapical lesion size was further measured with micro-computed tomographic imaging. The number of osteoclasts was also counted by tartrate-resistant acid phosphatase histoenzymology. Real-time polymerase chain reaction and immunohistochemistry were used to analyze the expression levels of receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), MMP-2, and MMP-8.

Results: There was a significant difference (P < .05) between the 2 types of animals regarding the periapical lesion size, which was larger in MMP-9 KO animals. No significant differences (P > .05) were found between WT and MMP-9 KO mice related to the osteoclast number as well as the pulpal, apical, and periapical features. More neutrophil cells were observed in MMP-9 KO animals than WT mice (P < .05). The expression levels of RANK, RANKL, OPG, IL-1β, TNF-α, MMP-2, and MMP-8 were found up-regulated in MMP-9 KO mice (P < .05).

Conclusions: MMP-9 KO animals developed larger periapical lesions with greater inflammatory response, indicating an important role of MMP-9 in the host's immune and inflammatory response to root canal and periradicular infection.

Keywords: Inflammatory response; knockout mice; matrix metalloproteinase-9; periapical lesion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / analysis
  • Animals
  • Cell Count
  • Dental Pulp Exposure / complications
  • Disease Progression
  • Interleukin-1beta / analysis
  • Isoenzymes / analysis
  • Male
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 8 / analysis
  • Matrix Metalloproteinase 9 / deficiency*
  • Mice
  • Mice, Knockout
  • Neutrophils / pathology
  • Osteoclasts / pathology
  • Osteoprotegerin / analysis
  • Periapical Periodontitis / enzymology*
  • Periapical Periodontitis / pathology
  • RANK Ligand / analysis
  • Receptor Activator of Nuclear Factor-kappa B / analysis
  • Tartrate-Resistant Acid Phosphatase
  • Tumor Necrosis Factor-alpha / analysis
  • X-Ray Microtomography / methods

Substances

  • Interleukin-1beta
  • Isoenzymes
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • MMP8 protein, mouse
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse