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Phytocystatin CsinC...
Phytocystatin CsinCPI-2 Reduces Osteoclastogenesis and Alveolar Bone Loss
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Leguizamon, N. D. (author)
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de Molo, R. S. (author)
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Coletto-Nunes, G. (author)
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Nogueira, A. V. B. (author)
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Rocha, S. V. (author)
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Neo-Justino, D. M. (author)
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Soares-Costa, A. (author)
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Cerri, P. S. (author)
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- Lerner, Ulf H (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Souza, P. P. C. (author)
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Cirelli, J. A. (author)
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(creator_code:org_t)
- 2021-07-30
- 2022
- English.
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In: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 101:2, s. 216-225
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Odontologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dentistry (hsv//eng)
Keyword
- periodontal diseases
- periodontitis
- bone resorption
- osteoclasts
- inflammation
- cystatins
- resorption in-vitro
- factor-kappa-b
- periodontal-disease
- cystatin-c
- sugarcane cystatin
- osteoimmunology
- osteonecrosis
- activation
- expression
- cytokines
- Dentistry
- Oral Surgery & Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Leguizamon, N. D ...
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de Molo, R. S.
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Coletto-Nunes, G ...
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Nogueira, A. V. ...
-
Rocha, S. V.
-
Neo-Justino, D. ...
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show more...
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Soares-Costa, A.
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Cerri, P. S.
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Lerner, Ulf H
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Souza, P. P. C.
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Cirelli, J. A.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Dentistry
- Articles in the publication
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Journal of Denta ...
- By the university
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University of Gothenburg