hytocystatin CsinCPI-2 Reduces Osteoclastogenesis and Alveolar Bone Los

Autor(es):Mostrar menos -

Leguizamon, N. Da Ponte ^[1] ; de Molo, R. S. ^[1] ; Coletto-Nunes, G. ^[1] ; Nogueira, A. V. B. ^[2] ; Rocha, V, S. ; Neo-Justino, D. M. ^[3] ; Soares-Costa, A. ^[3] ; Cerri, P. S. ^[4] ; Lerner, U. H. ^[5] ; Souza, P. P. C. ^[6] ; Cirelli, J. A. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Dent, Dept Diag & Surg, Rua Humaita 1680, BR-14801903 Araraquara, SP - Brazil

^[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Periodontol & Operat Dent, Mainz - Germany

^[3] Rocha, S., V, Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos - Brazil

^[4] Sao Paulo State Univ UNESP, Dept Morphol Genet Orthodont & Pediat Dent, Araraquara, SP - Brazil

^[5] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Dept Internal Med & Clin N, Gothenburg - Sweden

^[6] Univ Fed Goias, Fac Dent, Innovat Biomat Lab, Av Univ Esq 1a Ave S-N, BR-74605220 Goiania, Go - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF DENTAL RESEARCH; v. 101, n. 2 JUL 2021.
• Citações Web of Science: 1

Resumo

Periodontal disease (PD) is a polymicrobial chronic inflammatory condition of the supporting tissues around the teeth, leading to the destruction of surrounding connective tissue. During the progression of PD, osteoclasts play a crucial role in the resorption of alveolar bone that eventually leads to the loss of teeth if the PD is left untreated. Therefore, the development of antiresorptive therapies targeting bone-resorbing cells will significantly benefit the treatment of PD. Here, we demonstrate the inhibitory effect of CsinCPI-2, a novel cysteine peptidase inhibitor from the orange tree, on periodontitis-induced inflammation, alveolar bone loss, and osteoclast differentiation. Using the ligature-induced periodontitis model in mice, we show that treatment with CsinCPI-2 (0.8 mu g/g of body weight) significantly reduced inflammatory cell infiltrate in the connective tissue and prevented the loss of alveolar bone mass (BV/TV) caused by PD, effects associated with diminished numbers of TRAP-positive multinucleated cells. Furthermore, CsinCPI-2 significantly downregulated the numbers of inflammatory cells expressing CD3, CD45, MAC387, and IL-1 beta. In vitro, CsinCPI-2 inhibited RANKL-induced TRAP+ multinucleated osteoclast formation in mouse bone marrow macrophage cultures in a concentration-dependent manner. This effect was not due to cytotoxicity, as demonstrated by the MTT assay. CsinCPI-2 inhibited RANKL-induced mRNA expression of Acp5, Calcr, and Ctsk, as well as the RANKL-induced upregulation of Nfatc1, a crucial transcription factor for osteoclast differentiation. Based on our findings, CsinCPI-2 prevents bone loss induced by PD by controlling the inflammatory process and acting directly on osteoclastogenesis, suggesting an interesting potential for CsinCPI-2 in the strategy for PD treatment. (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: 18/10727-9 - Fitocistatina Csin-CPI-2 como possível candidato terapêutico para o tratamento da doença periodontal e artrite reumatoide
• Beneficiário: Ewelin Gabrielle Cardoso Goes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
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• Beneficiário: Ana Carolina Cindio
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/09876-4 - Periodontite e Artrite Reumatoide - Associação, Duplo Tratamento e Resolução
• Beneficiário: Rafael Scaf de Molon
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
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• Beneficiário: Rafael Scaf de Molon
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado