Abstract
Introduction
The aim of this study was to characterize the formation and progression of experimentally
induced periapical lesions in TLR2 knockout (TLR2 KO) mice.
Methods
Periapical lesions were induced in molars of 28 wild type (WT) and 27 TLR2 KO mice.
After 7, 21, and 42 days, the animals were euthanized, and the mandibles were subjected
to histotechnical processing. Hematoxylin-eosin–stained sections were examined under
conventional light microscopy for the description of pulpal, apical, and periapical
features and under fluorescence microscopy for the determination of the periapical
lesion size. The subsequent sections were evaluated by tartrate resistant acid phosphatase
histoenzymology (osteoclasts), Brown and Brenn staining (bacteria), and immunohistochemistry
(RANK, RANKL, and OPG). Data were analyzed by the Mann-Whitney U and Kruskal-Wallis tests (α = 0.05).
Results
The WT group showed significant differences (P < .05) in the periapical lesion size and the osteoclast number between 7 and 42 days
and between 21 and 42 days. In the TLR2 KO group, significant differences (P < .05) in the periapical lesion size and the osteoclast number were found between
7 days and the other periods. There was a significant difference (P < .05) between the 2 types of animal regarding the periapical lesion size, which
was larger in the TLR2 KO animals. No significant differences (P > .05) were found between WT and TLR2 KO mice related to the pulpal, apical, and
periapical features; bacteria localization; and immunohistochemical results (except
for RANK expression).
Conclusions
TLR2 KO animals developed larger periapical lesions with a greater number of osteoclasts,
indicating the important role of this receptor in the host's immune and inflammatory
response to root canal and periradicular infection.
Key Words
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References
- Roles of TLR2, TLR4, NOD2, and NOD1 in pulp fibroblasts.J Dent Res. 2009; 88: 762-767
- The roles of TLRs, RLRs and NLRs in pathogen recognition.Int Immunol. 2009; 21: 317-337
- Toll-like receptors stimulate human neutrophil function.Blood. 2003; 102: 2660-2669
- Lipopolysaccharide and double-stranded RNA up-regulate toll-like receptor 2 independently of myeloid differentiation factor 88.J Biol Chem. 2004; 279: 39727-39735
- Taking a toll on the bones: regulation of bone metabolism by innate immune regulators.Autoimmunity. 2008; 41: 195-203
- Toll-like receptors in innate immunity.Int Immunol. 2005; 17: 1-14
- A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.Nature. 1997; 388: 394-397
- Toll-like receptors and innate immunity.Nat Rev Immunol. 2001; 1 (135–5)
- Cytokine production by human odontoblast-like cells upon Toll-like receptor-2 engagement.Immunobiology. 2011; 216: 513-517
- Discrimination of bacterial lipoproteins by Toll-like receptor 6.Int Immunol. 2001; 13: 933-940
- Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins.J Immunol. 2002; 169: 10-14
- Blockade of TLR2 inhibits Porphyromonas gingivalis suppression of mineralized matrix formation by human dental pulp stem cells.J Endod. 2011; 37: 812-818
- Porphyromonas endodontalis lipopolysaccharides induce RANKL by mouse osteoblast in a way different from that of Escherichia coli lipopolysaccharide.J Endod. 2011; 37: 1653-1658
- Role of MD-2 in TLR2- and TLR4-mediated recognition of Gram-negative and Gram-positive bacteria and activation of chemokine genes.J Endotoxin Res. 2000; 6: 401-405
- Pathogen recognition and innate immunity.Cell. 2006; 124: 783-801
- TLRs and innate immunity.Blood. 2009; 113: 1399-1407
- Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells.J Immunol. 2003; 170: 1625-1629
- Gene expression analysis of resident macrophages in lipopolysaccharide-stimulated rat molar pulps.J Endod. 2011; 37: 1258-1263
- TLR2 is expressed on activated T cells as a costimulatory receptor.Proc Natl Acad Sci U S A. 2004; 101: 3029-3034
- Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells.Proc Natl Acad Sci U S A. 2006; 103: 7048-7053
- B and CD4+ T-cell expression of TLR2 is critical for optimal induction of a T-cell-dependent humoral immune response to intact Streptococcus pneumoniae.Eur J Immunol. 2008; 38: 3316-3326
- Different roles of odontoblasts and fibroblasts in immunity.J Dent Res. 2008; 87: 256-261
- Toll-like receptor 2 activation by lipoteichoic acid induces differential production of pro-inflammatory cytokines in human odontoblasts, dental pulp fibroblasts and immature dendritic cells.Immunobiology. 2010; 215: 53-59
- Increased gene expression of toll-like receptors and antigen-presenting cell-related molecules in the onset of experimentally induced furcation lesions of endodontic origin in rat molars.J Endod. 2010; 36: 251-255
- Toll-like receptor 2 expression in refractory periapical lesions.Int Endod J. 2011; 44: 907-916
- Interferon-gamma, interleukin-10, Intercellular adhesion molecule-1, and chemokine receptor 5, but not interleukin-4, attenuate the development of periapical lesions.J Endod. 2008; 34: 31-38
- Antimicrobial photodynamic therapy for the treatment of teeth with apical periodontitis: a histopathological evaluation.J Endod. 2012; 38: 360-366
- Application of fluorescence microscopy on hematoxylin and eosin-stained sections of healthy and diseased teeth and supporting structures.J Oral Pathol Med. 2007; 36: 377-381
- A method for the differential staining of Gram-positive and Gram-negative bacteria in tissue sections.Bull. Johns Hopkins Hosp. 1931; 48: 69-73
- Overexpressing autoimmune regulator regulates the expression of toll-like receptors by interacting with their promoters in RAW264.7 cells.Cell Immunol. 2011; 270: 156-163
- Toll-like receptor 4-deficient mice have reduced bone destruction following mixed anaerobic infection.Infect Immun. 2000; 68: 4681-4687
- The role of toll-like receptor 2 in the recognition of Aggregatibacter actinomycetemcomitans.J Periodontol. 2009; 80: 2010-2019
- TLR signaling.Cell Death Differ. 2006; 13: 816-825
- The negative regulation of Toll-like receptor and associated pathways.Immunol Cell Biol. 2007; 85: 425-434
- Review of osteoimmunology and the host response in endodontic and periodontal lesions.J Oral Microbiol. 2011; 17: 3
- CCR2 deficiency results in increased osteolysis in experimental periapical lesions in mice.J Endod. 2010; 36: 244-250
- RANKL in human periapical granuloma: possible involvement in periapical bone destruction.Oral Dis. 2006; 12: 283-289
- Kinetics of RANKL, RANK and OPG expressions in experimentally induced rat periapical lesions.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 103: 707-711
- Differential patterns of receptor activator of nuclear factor kappa B ligand/osteoprotegerin expression in human periapical granulomas: possible association with progressive or stable nature of the lesions.J Endod. 2008; 34: 932-938
- Comparative immunohistochemical expression of RANK, RANKL and OPG in radicular and dentigerous cysts.Arch Oral Biol. 2011; 56: 1256-1263
Article info
Publication history
Published online: April 30, 2012
Footnotes
This study is part of the master's dissertation of the second author (P.D.F.F.), who received a scholarship from the Brazilian Ministry of Health's Federal Agency for Support and Evaluation of Graduate Education (CAPES).
Identification
Copyright
© 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.