MMP9 deficiency increased the size of experimentally induced apical periodontitis.
BACKGROUND
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.
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Chunyan
C
Wan
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Guohua
G
Yuan
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Jingwen
J
Yang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Qin
Q
Sun
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Li
L
Zhang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Jie
J
Zhang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Lu
L
Zhang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: zhichen@whu.edu.cn.
Zhi
Z
Chen
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D002452:Cell Count; D003789:Dental Pulp Exposure / Q000150:complications; D018450:Disease Progression; D053583:Interleukin-1beta / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020784:Matrix Metalloproteinase 8 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis; D010485:Periapical Periodontitis / Q000201:enzymology* / Q000473:pathology; D053245:RANK Ligand / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055114:X-Ray Microtomography / Q000379:methods
D053583:Interleukin-1beta; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
Inflammatory response; knockout mice; matrix metalloproteinase-9; periapical lesion