Pam2CSK4 (TLR2 agonist) induces periodontal destruction in mice.

Abstract

Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.

• Authors: João Antonio Chaves de Souza, Fernando Augusto Cintra Magalhães, Guilherme Jose Pimentel Lopes de Oliveira, Rafael Scaf DE Molon, José Antonio Zuanon, Pedro Paulo Chaves de Souza
• Journal: Brazilian oral research (Braz Oral Res) Vol. 34 Pg. e012 ( 2020) ISSN: 1807-3107 [Electronic] Brazil
• PMID: 32049112 (Publication Type: Journal Article)

Chemical References

• Lipopeptides
• Pam2CSK4 lipopeptide
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Tartrate-Resistant Acid Phosphatase

Topics

• Alveolar Bone Loss (etiology, pathology)
• Alveolar Process (drug effects, pathology)
• Animals
• Disease Models, Animal
• Gingiva (drug effects, pathology)
• Gingivitis (etiology, pathology)
• Lipopeptides (pharmacology)
• Male
• Mice, Inbred C57BL
• Osteoclasts (drug effects, physiology)
• Periodontitis (etiology, microbiology, pathology)
• Random Allocation
• Tartrate-Resistant Acid Phosphatase
• Time Factors
• Toll-Like Receptor 2 (antagonists & inhibitors)
• X-Ray Microtomography