In vivo and in vitro anti-inflammatory and pro-osteogenic effects of citrus cystatin CsinCPI-2

Detalhes bibliográficos
Autor(a) principal: Leguizamón, Natalia Da Ponte [UNESP]
Data de Publicação: 2019
Outros Autores: 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]
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.
id UNSP_d05f5cafae8947c2f4e87b810dae3b84
oai_identifier_str oai:repositorio.unesp.br:11449/189260
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling 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