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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Phytocystatin CsinCPI-2 Reduces Osteoclastogenesis and Alveolar Bone Loss

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Author(s):
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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]
Total Authors: 11
Affiliation:
[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
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF DENTAL RESEARCH; JUL 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 15/21697-5 - A potentially new class of bone-protective drugs, phytocystatin from sweet orange Csin-CPI-2, as possible therapeutic candidate for treatment of bone diseases.
Grantee:Rafael Scaf de Molon
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/09876-4 - Periodontitis and Rheumatoid Arthritis - Association, Dual Treatment and Resolution
Grantee:Rafael Scaf de Molon
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 18/10727-9 - Phytocystatins Csin-CPI-2 as a possible therapeutic candidate for treatment of periodontal disease and rheumatoid arthritis
Grantee:Ewelin Gabrielle Cardoso Goes
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/10728-5 - A new therapeutic approach to inhibit bone loss using phytocystatin Csin-CPI-2 for the treatment of metabolic bone diseases
Grantee:Ana Carolina Cindio
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 14/05283-3 - The effect of bradykinin on osteoclastogenesis in vitro and LPS-induced bone resorption in vivo
Grantee:Pedro Paulo Chaves de Souza
Support type: Research Grants - Young Investigators Grants