MMP9 deficiency increased the size of experimentally induced apical periodontitis

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.