Pam2CSK4 (TLR2 agonist) induces periodontal destruction in mice

Autor(es)

João Antonio Chaves de SOUZA ^[1] ; Fernando Augusto Cintra MAGALHÃES ^[2] ; Guilherme Jose Pimentel Lopes de OLIVEIRA ^[3] ; Rafael Scaf DE MOLON ^[4] ; José Antonio ZUANON ^[5] ; Pedro Paulo Chaves de SOUZA ^[6]

Afiliação do(s) autor(es)

^[1] Universidade Federal de Goiás. School of Dentistry. Department of Periodontology - Brasil

^[2] Universidade Federal do Maranhão. Department of Nursing - Brasil

^[3] Universidade Federal de Uberlândia. School of Dentistry. Department of Periodontology - Brasil

^[4] Universidade Estadual Paulista. School of Dentistry. Department of Diagnosis and Surgery - Brasil

^[5] Universidade Estadual Paulista. School of Dentistry. Department of Physiology and Pathology - Brasil

^[6] Universidade Federal de Goiás. School of Dentistry. Department of Stomatology - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Oral Research; v. 34, 2020-02-10.

Resumo

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. (AU)

• Processo FAPESP: 14/05283-3 - Influência da bradicinina sobre a osteoclastogênese in vitro e sobre a reabsorção óssea induzida por LPS in vivo
• Beneficiário: Pedro Paulo Chaves de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/21697-5 - Uma potencial nova classe de droga para inibir a reabsorção óssea, fitocistatina Csin-CPI-2 derivada da laranja, como possível candidato terapêutico para tratamento de doenças ósseas.
• Beneficiário: Rafael Scaf de Molon
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado