In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.cyto.2019.154760 http://hdl.handle.net/11449/189260 |
Resumo: | Cystatins are natural inhibitors of cysteine peptidases. Recently, cystatins derived from plants, named phytocystatins, have been extensively studied. Among them, CsinCPI-2 proteins from Citrus sinensis were identified and recombinantly produced by our group. Thus, this study described the recombinant expression, purification, and inhibitory activity of this new phytocystatin against human cathepsins K and B and assessed the anti-inflammatory effect of CsinCPI-2 in vitro in mouse and in vivo in rats. In addition, the pro-osteogenic effect of CsinCPI-2 was investigated in vitro. The inflammatory response of mouse macrophage cells stimulated with P. gingivalis was modulated by CsinCPI-2. The in vitro results showed an inhibitory effect (p < 0.05) on cathepsin K, cathepsin B, IL-1β, and TNF-α gene expression. In addition, CsinCPI-2 significantly inhibited in vivo the activity of TNF-α (p < 0.05) in the blood of rats, previously stimulated by E. coli lipopolysaccharide (LPS). CsinCPI-2 had a pro-osteogenic effect in human dental pulp cells, demonstrated by the increase in alkaline phosphatase (ALP) activity, deposition of mineralized nodules, and the gene expression of the osteogenic markers as bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (Runx-2), ALP, osteocalcin, and bone sialoprotein (BSP). These preliminary studies suggested that CsinCPI-2 has a potential anti-inflammatory, and at the same time, a pro-osteogenic effect. This may lead to new therapies for the control of diseases where inflammation plays a key role, such as periodontal disease and apical periodontitis. |
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In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2CathepsinsCystatinsCysteine proteinasesCytokinesCystatins are natural inhibitors of cysteine peptidases. Recently, cystatins derived from plants, named phytocystatins, have been extensively studied. Among them, CsinCPI-2 proteins from Citrus sinensis were identified and recombinantly produced by our group. Thus, this study described the recombinant expression, purification, and inhibitory activity of this new phytocystatin against human cathepsins K and B and assessed the anti-inflammatory effect of CsinCPI-2 in vitro in mouse and in vivo in rats. In addition, the pro-osteogenic effect of CsinCPI-2 was investigated in vitro. The inflammatory response of mouse macrophage cells stimulated with P. gingivalis was modulated by CsinCPI-2. The in vitro results showed an inhibitory effect (p < 0.05) on cathepsin K, cathepsin B, IL-1β, and TNF-α gene expression. In addition, CsinCPI-2 significantly inhibited in vivo the activity of TNF-α (p < 0.05) in the blood of rats, previously stimulated by E. coli lipopolysaccharide (LPS). CsinCPI-2 had a pro-osteogenic effect in human dental pulp cells, demonstrated by the increase in alkaline phosphatase (ALP) activity, deposition of mineralized nodules, and the gene expression of the osteogenic markers as bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (Runx-2), ALP, osteocalcin, and bone sialoprotein (BSP). These preliminary studies suggested that CsinCPI-2 has a potential anti-inflammatory, and at the same time, a pro-osteogenic effect. This may lead to new therapies for the control of diseases where inflammation plays a key role, such as periodontal disease and apical periodontitis.ASCRS Research FoundationCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Diagnosis and Surgery School of Dentistry at Araraquara Sao Paulo State University – UNESP, AraraquaraDepartment of Restorative Dentistry School of Dentistry at Araraquara Sao Paulo State University – UNESP, AraraquaraHealth Sciences Institute Federal University of Mato Grosso – UFMTDepartment of Genetic and Evolution Federal University of Sao CarlosDepartment of Chemistry and Biochemistry Laboratory of Bioassays and Cell Dynamics Institute of Biosciences Sao Paulo State University – UNESP, BotucatuDepartment of Diagnosis and Surgery School of Dentistry at Araraquara Sao Paulo State University – UNESP, AraraquaraDepartment of Restorative Dentistry School of Dentistry at Araraquara Sao Paulo State University – UNESP, AraraquaraDepartment of Chemistry and Biochemistry Laboratory of Bioassays and Cell Dynamics Institute of Biosciences Sao Paulo State University – UNESP, BotucatuCAPES: 2016/1604159FAPESP: 2017/05784-0CNPq: 486335/2013-5Universidade Estadual Paulista (Unesp)Federal University of Mato Grosso – UFMTUniversidade Federal de São Carlos (UFSCar)Leguizamón, Natalia Da Ponte [UNESP]Rodrigues, Elisandra Marcia [UNESP]de Campos, Michel LeandroNogueira, Andressa Vilas Boas [UNESP]Viola, Kennia Scapin [UNESP]Schneider, Vanessa KarineNeo-Justino, Daniela MorilhaTanomaru-Filho, Mario [UNESP]Zambuzzi, Willian Fernando [UNESP]Henrique-Silva, FlavioSoares-Costa, AndreaFaria, Gisele [UNESP]Cirelli, Joni Augusto [UNESP]2019-10-06T16:35:05Z2019-10-06T16:35:05Z2019-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.cyto.2019.154760Cytokine, v. 123.1096-00231043-4666http://hdl.handle.net/11449/18926010.1016/j.cyto.2019.1547602-s2.0-85067364691Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCytokineinfo:eu-repo/semantics/openAccess2024-09-27T18:05:03Zoai:repositorio.unesp.br:11449/189260Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-27T18:05:03Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
title |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
spellingShingle |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 Leguizamón, Natalia Da Ponte [UNESP] Cathepsins Cystatins Cysteine proteinases Cytokines |
title_short |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
title_full |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
title_fullStr |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
title_full_unstemmed |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
title_sort |
In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2 |
author |
Leguizamón, Natalia Da Ponte [UNESP] |
author_facet |
Leguizamón, Natalia Da Ponte [UNESP] Rodrigues, Elisandra Marcia [UNESP] de Campos, Michel Leandro Nogueira, Andressa Vilas Boas [UNESP] Viola, Kennia Scapin [UNESP] Schneider, Vanessa Karine Neo-Justino, Daniela Morilha Tanomaru-Filho, Mario [UNESP] Zambuzzi, Willian Fernando [UNESP] Henrique-Silva, Flavio Soares-Costa, Andrea Faria, Gisele [UNESP] Cirelli, Joni Augusto [UNESP] |
author_role |
author |
author2 |
Rodrigues, Elisandra Marcia [UNESP] de Campos, Michel Leandro Nogueira, Andressa Vilas Boas [UNESP] Viola, Kennia Scapin [UNESP] Schneider, Vanessa Karine Neo-Justino, Daniela Morilha Tanomaru-Filho, Mario [UNESP] Zambuzzi, Willian Fernando [UNESP] Henrique-Silva, Flavio Soares-Costa, Andrea Faria, Gisele [UNESP] Cirelli, Joni Augusto [UNESP] |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Federal University of Mato Grosso – UFMT Universidade Federal de São Carlos (UFSCar) |
dc.contributor.author.fl_str_mv |
Leguizamón, Natalia Da Ponte [UNESP] Rodrigues, Elisandra Marcia [UNESP] de Campos, Michel Leandro Nogueira, Andressa Vilas Boas [UNESP] Viola, Kennia Scapin [UNESP] Schneider, Vanessa Karine Neo-Justino, Daniela Morilha Tanomaru-Filho, Mario [UNESP] Zambuzzi, Willian Fernando [UNESP] Henrique-Silva, Flavio Soares-Costa, Andrea Faria, Gisele [UNESP] Cirelli, Joni Augusto [UNESP] |
dc.subject.por.fl_str_mv |
Cathepsins Cystatins Cysteine proteinases Cytokines |
topic |
Cathepsins Cystatins Cysteine proteinases Cytokines |
description |
Cystatins are natural inhibitors of cysteine peptidases. Recently, cystatins derived from plants, named phytocystatins, have been extensively studied. Among them, CsinCPI-2 proteins from Citrus sinensis were identified and recombinantly produced by our group. Thus, this study described the recombinant expression, purification, and inhibitory activity of this new phytocystatin against human cathepsins K and B and assessed the anti-inflammatory effect of CsinCPI-2 in vitro in mouse and in vivo in rats. In addition, the pro-osteogenic effect of CsinCPI-2 was investigated in vitro. The inflammatory response of mouse macrophage cells stimulated with P. gingivalis was modulated by CsinCPI-2. The in vitro results showed an inhibitory effect (p < 0.05) on cathepsin K, cathepsin B, IL-1β, and TNF-α gene expression. In addition, CsinCPI-2 significantly inhibited in vivo the activity of TNF-α (p < 0.05) in the blood of rats, previously stimulated by E. coli lipopolysaccharide (LPS). CsinCPI-2 had a pro-osteogenic effect in human dental pulp cells, demonstrated by the increase in alkaline phosphatase (ALP) activity, deposition of mineralized nodules, and the gene expression of the osteogenic markers as bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (Runx-2), ALP, osteocalcin, and bone sialoprotein (BSP). These preliminary studies suggested that CsinCPI-2 has a potential anti-inflammatory, and at the same time, a pro-osteogenic effect. This may lead to new therapies for the control of diseases where inflammation plays a key role, such as periodontal disease and apical periodontitis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T16:35:05Z 2019-10-06T16:35:05Z 2019-11-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.cyto.2019.154760 Cytokine, v. 123. 1096-0023 1043-4666 http://hdl.handle.net/11449/189260 10.1016/j.cyto.2019.154760 2-s2.0-85067364691 |
url |
http://dx.doi.org/10.1016/j.cyto.2019.154760 http://hdl.handle.net/11449/189260 |
identifier_str_mv |
Cytokine, v. 123. 1096-0023 1043-4666 10.1016/j.cyto.2019.154760 2-s2.0-85067364691 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cytokine |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1813546524079030272 |