Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration

Detalhes bibliográficos
Autor(a) principal: Kobrock, Anna Laura Fernandes
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/34824
Resumo: Dental caries is a highly prevalent chronic disease in humans and represents a global public health challenge, with a prevalence of 49- 83%, being associated with a high morbidity and extensive healthcare costs. Current state-of-art therapeutic strategies, used in more advanced caries that reach the dental pulp, are technically demanding and invasive procedures that involve pulpectomy and root canal treatment, aiming for a reparative outcome that does not allow the regeneration of the lost tissues. The dental pulp has a reparative and, as well, a regenerative potential, in which, after damage, signalling cascades may be activated to promote cell adhesion, proliferation, migration, angiogenesis and differentiation of precursor cells, leading to the regeneration of the lost dental tissues. Despite the acknowledgement, the putative manipulation of biological pathways to prime pulp regeneration is still largely unknown. Protein phosphatase 1 (PP1) is a serine/threonine phosphatase that plays a fundamental role in cell regulation through the removal of phosphate groups from serine/threonine residues. A recent study suggests that PP1 activation in odontoblasts may induce osteogenic/odontogenic differentiation, modulating therefore dental pulp repair and regeneration. In this sense, the mail goal of this work is to use a disrupting peptide - MSS1 that has been reported to disrupt PP1 interactions, making PP1 active to modulate PP1-related signalling, and potentially promote dental pulp regeneration. The results showed that, in vitro, MSS1 induced cell proliferation in early stages of dental pulp stromal cells’ cultures, and in mid-late stages, enhanced osteogenic/odontogenic differentiation, suggesting its potential to modulate dental pulp repair and regeneration. In conclusion, this work demonstrated the potential use of MSS1 to modulate PP1 signalling in dental pulp cells, eventually assisting on tissue regeneration, as a potential and innovative, non-invasive therapeutic strategy to treat pulp-related lesions.
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spelling Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regenerationDental pulp stromal cellsOsteogenic/odontogenic differentiationDisrupting peptideProtein phosphatase 1RegenerationDental caries is a highly prevalent chronic disease in humans and represents a global public health challenge, with a prevalence of 49- 83%, being associated with a high morbidity and extensive healthcare costs. Current state-of-art therapeutic strategies, used in more advanced caries that reach the dental pulp, are technically demanding and invasive procedures that involve pulpectomy and root canal treatment, aiming for a reparative outcome that does not allow the regeneration of the lost tissues. The dental pulp has a reparative and, as well, a regenerative potential, in which, after damage, signalling cascades may be activated to promote cell adhesion, proliferation, migration, angiogenesis and differentiation of precursor cells, leading to the regeneration of the lost dental tissues. Despite the acknowledgement, the putative manipulation of biological pathways to prime pulp regeneration is still largely unknown. Protein phosphatase 1 (PP1) is a serine/threonine phosphatase that plays a fundamental role in cell regulation through the removal of phosphate groups from serine/threonine residues. A recent study suggests that PP1 activation in odontoblasts may induce osteogenic/odontogenic differentiation, modulating therefore dental pulp repair and regeneration. In this sense, the mail goal of this work is to use a disrupting peptide - MSS1 that has been reported to disrupt PP1 interactions, making PP1 active to modulate PP1-related signalling, and potentially promote dental pulp regeneration. The results showed that, in vitro, MSS1 induced cell proliferation in early stages of dental pulp stromal cells’ cultures, and in mid-late stages, enhanced osteogenic/odontogenic differentiation, suggesting its potential to modulate dental pulp repair and regeneration. In conclusion, this work demonstrated the potential use of MSS1 to modulate PP1 signalling in dental pulp cells, eventually assisting on tissue regeneration, as a potential and innovative, non-invasive therapeutic strategy to treat pulp-related lesions.A cárie dentária é uma doença crónica de elevada prevalência, que representa um desafio global de saúde publica, com uma prevalência de 49-83%, estando associada a uma elevada morbilidade e elevados custos de saúde. As estratégias terapêuticas atualmente utilizadas nas lesões de cárie mais avançadas, que atingem a polpa dentária, são procedimentos tecnicamente exigentes e invasivos, que envolvem a pulpectomia e o tratamento endodôntico radical, visando um resultado reparador que não permite a regeneração dos tecidos danificados. A polpa dentária possui, no entanto, um potencial reparativo e regenerativo após o dano, em que distintas vias de sinalização podem ser ativadas para promover processo biológicos como a adesão celular, proliferação, migração, angiogénese e diferenciação que células precursoras, levando à regeneração dos tecidos danificados. Apesar do reconhecimento destes processos, a manipulação das vias biológicas para promoção da regeneração pulpar ainda é essencialmente desconhecida. A proteína fosfatase 1 (PP1) é uma fosfatase de serina/treonina que possui um papel fundamental na regulação celular através da remoção de grupos fosfato de resíduos de serina/treonina. Um estudo recente sugere que a ativação da PP1 em odontoblastos pode induzir a diferenciação osteogénica/odontogénica, modulando, assim, a reparação e a regeneração da polpa dentária. Neste sentido, o principal objetivo deste trabalho assenta na utilização de um péptido disruptivo- MSS1, com atividade de disrupção das interações da PP1, tornando-a ativa para modular as vias de sinalização associadas à PP1, e potencialmente promover a regeneração da polpa dentária. Os resultados demonstram que, in vitro, o MSS1 induz a proliferação celular em fases iniciais de culturas de células estromais da polpa dentária e, em fases intermédias-tardias, aumenta a diferenciação osteogénica/odontogénica, sugerindo o seu potencial para modular a reparação e regeneração da polpa dentária. Em jeito de conclusão, este trabalho demonstrou o potencial uso do MSS1 para modular a sinalização da PP1 nas células estromais da polpa dentária, eventualmente suportando a regeneração dos tecidos, como uma estratégia terapêutica inovadora e não-invasiva para tratar lesões polpares.2022-09-28T15:33:44Z2022-07-26T00:00:00Z2022-07-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/34824engKobrock, Anna Laura Fernandesinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:07:04Zoai:ria.ua.pt:10773/34824Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:05:58.002665Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
title Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
spellingShingle Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
Kobrock, Anna Laura Fernandes
Dental pulp stromal cells
Osteogenic/odontogenic differentiation
Disrupting peptide
Protein phosphatase 1
Regeneration
title_short Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
title_full Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
title_fullStr Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
title_full_unstemmed Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
title_sort Protein phosphatase 1 disrupting peptide as potential modulator of dental pulp regeneration
author Kobrock, Anna Laura Fernandes
author_facet Kobrock, Anna Laura Fernandes
author_role author
dc.contributor.author.fl_str_mv Kobrock, Anna Laura Fernandes
dc.subject.por.fl_str_mv Dental pulp stromal cells
Osteogenic/odontogenic differentiation
Disrupting peptide
Protein phosphatase 1
Regeneration
topic Dental pulp stromal cells
Osteogenic/odontogenic differentiation
Disrupting peptide
Protein phosphatase 1
Regeneration
description Dental caries is a highly prevalent chronic disease in humans and represents a global public health challenge, with a prevalence of 49- 83%, being associated with a high morbidity and extensive healthcare costs. Current state-of-art therapeutic strategies, used in more advanced caries that reach the dental pulp, are technically demanding and invasive procedures that involve pulpectomy and root canal treatment, aiming for a reparative outcome that does not allow the regeneration of the lost tissues. The dental pulp has a reparative and, as well, a regenerative potential, in which, after damage, signalling cascades may be activated to promote cell adhesion, proliferation, migration, angiogenesis and differentiation of precursor cells, leading to the regeneration of the lost dental tissues. Despite the acknowledgement, the putative manipulation of biological pathways to prime pulp regeneration is still largely unknown. Protein phosphatase 1 (PP1) is a serine/threonine phosphatase that plays a fundamental role in cell regulation through the removal of phosphate groups from serine/threonine residues. A recent study suggests that PP1 activation in odontoblasts may induce osteogenic/odontogenic differentiation, modulating therefore dental pulp repair and regeneration. In this sense, the mail goal of this work is to use a disrupting peptide - MSS1 that has been reported to disrupt PP1 interactions, making PP1 active to modulate PP1-related signalling, and potentially promote dental pulp regeneration. The results showed that, in vitro, MSS1 induced cell proliferation in early stages of dental pulp stromal cells’ cultures, and in mid-late stages, enhanced osteogenic/odontogenic differentiation, suggesting its potential to modulate dental pulp repair and regeneration. In conclusion, this work demonstrated the potential use of MSS1 to modulate PP1 signalling in dental pulp cells, eventually assisting on tissue regeneration, as a potential and innovative, non-invasive therapeutic strategy to treat pulp-related lesions.
publishDate 2022
dc.date.none.fl_str_mv 2022-09-28T15:33:44Z
2022-07-26T00:00:00Z
2022-07-26
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