Leguizamon, N. Da Ponte
de Molo, R. S.
Nogueira, A. V. B.
Rocha, V, S.
Neo-Justino, D. M.
Cerri, P. S.
Lerner, U. H.
Souza, P. P. C.
Cirelli, J. A.
Total Authors: 11
 Sao Paulo State Univ UNESP, Sch Dent, Dept Diag & Surg, Rua Humaita 1680, BR-14801903 Araraquara, SP - Brazil
 Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Periodontol & Operat Dent, Mainz - Germany
 Rocha, S., V, Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos - Brazil
 Sao Paulo State Univ UNESP, Dept Morphol Genet Orthodont & Pediat Dent, Araraquara, SP - Brazil
 Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Dept Internal Med & Clin N, Gothenburg - Sweden
 Univ Fed Goias, Fac Dent, Innovat Biomat Lab, Av Univ Esq 1a Ave S-N, BR-74605220 Goiania, Go - Brazil
Total Affiliations: 6
JOURNAL OF DENTAL RESEARCH;
Web of Science Citations:
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)