Abstract
Introduction
Periapical lesions are chronic inflammatory disorders of periradicular tissues caused
by etiologic agents of endodontic origin. The inflammatory chemokines are thought
to be involved in the latter observed osteolysis. With a murine model of experimental
periapical lesion, the objective of this study was to evaluate the role of the chemokine
receptor CCR2 in the lesion progression, osteoclast differentiation and activation,
and expression of inflammatory osteolysis-related mediators.
Methods
For lesion induction, right mandibular first molars were opened surgically with a
¼ carbine bur, and 4 bacterial strains were inoculated in the exposed dental pulp;
left mandibular first molars were used as controls. Animals were killed at 3, 7, 14,
and 21 days after surgeries to evaluate the kinetics of lesion development.
Results
CCR2 KO mice showed wider lesions than WT mice. CCR2 KO mice also expressed higher
levels of the osteoclastogenic and osteolytic factors, receptor activator of nuclear
factor kappa B ligand (RANKL) and cathepsin K, of the proinflammatory cytokine tumor
necrosis factor–alpha, and of the neutrophil migration related chemokine, KC.
Conclusions
These results suggest that CCR2 is important in host protection to periapical osteolysis.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of EndodonticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Kinetics of immune cell and bone resorptive responses to endodontic infections.J Endod. 1992; 18: 422-426
- Apical periodontitis: a dynamic encounter between root canal infection and host response.Periodontol 2000. 1997; 13: 121-148
- Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease.J Periodontal Res. 2003; 38: 210-217
- IL-18 enhances collagen-induced arthritis by recruiting neutrophils via TNF-alpha and leukotriene B4.J Immunol. 2003; 171: 1009-1015
- Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease.J Dent Res. 2007; 86: 306-319
- Differential expression of chemokines and chemokine receptors in inflammatory periapical diseases.Oral Microbiol Immunol. 2005; 20: 310-316
- Plasticity in tumor-promoting inflammation: impairment of macrophage recruitment evokes a compensatory neutrophil response.Neoplasia. 2008; 10: 329-340
- Recruitment of macrophages and polymorphonuclear leukocytes in Lyme carditis.Infect Immun. 2007; 75: 613-620
- Mycobacterium tuberculosis in chemokine receptor 2-deficient mice: influence of dose on disease progression.Infect Immun. 2002; 70: 5946-5954
- Analysis of corneal inflammation induced by cauterisation in CCR2 and MCP-1 knockout mice.Br J Ophthalmol. 2006; 90: 218-222
- Chemokine regulation of the inflammatory response to a low-dose influenza infection in CCR2-/- mice.J Leukoc Biol. 2007; 81: 793-801
- Differential in situ distribution of interleukin-8, monocyte chemoattractant protein-1 and Rantes in human chronic periapical granuloma.Oral Microbiol Immunol. 2000; 15: 63-65
- The role of chemokines in neutrophil biology.Front Biosci. 2008; 13: 2400-2407
- Induction of CXCR2 receptor by peroxisome proliferator-activated receptor gamma in human macrophages.Arterioscler Thromb Vasc Biol. 2008; 28: 932-939
- MCP-1 and RANTES are mediators of acute and chronic inflammation.Allergy Asthma Proc. 2001; 22: 133-137
- Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection.J Immunol. 2008; 180: 6846-6853
- Monocyte-mediated defense against microbial pathogens.Annu Rev Immunol. 2008; 26: 421-452
- MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATc1, and calcitonin receptor-positive but require receptor activator of NFkappaB ligand for bone resorption.J Biol Chem. 2006; 281: 1274-1285
- Macrophage-inflammatory protein-1alpha regulates preosteoclast differentiation in vitro.Biochem Biophys Res Commun. 1999; 254: 773-778
- MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation.J Biol Chem. 2005; 280: 16163-16169
- 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
- Kinetics of bone-resorbing activity in developing periapical lesions.J Dent Res. 1991; 70: 1362-1366
- iNOS-derived nitric oxide modulates infection-stimulated bone loss.J Dent Res. 2008; 87: 1155-1159
- Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans.Eur J Oral Sci. 2007; 115: 355-362
- Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP-1 and RANTES.J Cell Biochem. 2006; 97: 512-518
- PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro.Int J Cancer. 2007; 121: 724-733
- Osteoclast lineage and function.Arch Biochem Biophys. 2008; 473: 132-138
- The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction.J Periodontol. 2003; 74: 391-401
- Lipopolysaccharides (LPS) induce the differentiation of human monocytes to osteoclasts in a tumour necrosis factor (TNF) alpha-dependent manner: a link between infection and pathological bone resorption.Mol Immunol. 2008; 45: 3330-3337
- The potential role of suppressors of cytokine signaling in the attenuation of inflammatory reaction and alveolar bone loss associated with apical periodontitis.J Endod. 2008; 34: 1480-1484
- Dentin sialoprotein and phosphoprotein induce neutrophil recruitment: a mechanism dependent on IL-1beta, TNF-beta, and CXC chemokines.Calcif Tissue Int. 2004; 74: 532-541
- Neutrophil recruitment in immunized mice depends on MIP-2 inducing the sequential release of MIP-1alpha, TNF-alpha and LTB(4).Eur J Immunol. 2006; 36: 2025-2034
- Surface RANKL of Toll-like receptor 4-stimulated human neutrophils activates osteoclastic bone resorption.Blood. 2009; 114: 1633-1644
- The dual role of p55 tumour necrosis factor-alpha receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction.Clin Exp Immunol. 2007; 147: 128-138
- Monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, and RANTES recruit macrophages to the kidney in a mouse model of hemolytic-uremic syndrome.Infect Immun. 2007; 75: 1229-1236
- Mice lacking monocyte chemoattractant protein 1 have enhanced susceptibility to an interstitial polymicrobial infection due to impaired monocyte recruitment.Infect Immun. 2002; 70: 3164-3169
- Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice.J Clin Invest. 1997; 100: 2552-2561
- Human monocytes produce monocyte chemoattractant protein 1 (MCP-1) in response to a synthetic peptide derived from C-reactive protein.Clin Immunol Immunopathol. 1995; 74: 84-88
- Immunoregulatory role of ocular macrophages: the macrophages produce RANTES to suppress experimental autoimmune uveitis.J Immunol. 2003; 171: 2652-2659
Article info
Publication history
Published online: October 26, 2009
Identification
Copyright
© 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
