Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation.
Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4892678?pdf=render |
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| author | Carmen Herencia Juan Miguel Diaz-Tocados Lidia Jurado Addy Montes de Oca Maria Encarnación Rodríguez-Ortiz Carmen Martín-Alonso Julio M Martínez-Moreno Noemi Vergara Mariano Rodríguez Yolanda Almadén Juan R Muñoz-Castañeda |
| author_facet | Carmen Herencia Juan Miguel Diaz-Tocados Lidia Jurado Addy Montes de Oca Maria Encarnación Rodríguez-Ortiz Carmen Martín-Alonso Julio M Martínez-Moreno Noemi Vergara Mariano Rodríguez Yolanda Almadén Juan R Muñoz-Castañeda |
| author_sort | Carmen Herencia |
| collection | DOAJ |
| description | Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developing molecular therapies. Procaine is an anesthetic drug with demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt signaling of procaine was described in vitro in colon cancer cells.In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves these effects were also studied.Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic markers. In parallel, procaine inhibited canonical Wnt/β-catenin pathway, observing a loss of nuclear β-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3β and an increase of phosphorylated β-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3β, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3β and β-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed.Our results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/β-catenin pathway through the increase of Gsk3β expression and β-catenin phosphorylation. |
| first_indexed | 2024-12-10T11:43:56Z |
| format | Article |
| id | doaj.art-c62474a98a3d43048781fef9c528f37d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T11:43:56Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c62474a98a3d43048781fef9c528f37d2022-12-22T01:50:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015678810.1371/journal.pone.0156788Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation.Carmen HerenciaJuan Miguel Diaz-TocadosLidia JuradoAddy Montes de OcaMaria Encarnación Rodríguez-OrtizCarmen Martín-AlonsoJulio M Martínez-MorenoNoemi VergaraMariano RodríguezYolanda AlmadénJuan R Muñoz-CastañedaPeriodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developing molecular therapies. Procaine is an anesthetic drug with demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt signaling of procaine was described in vitro in colon cancer cells.In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves these effects were also studied.Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic markers. In parallel, procaine inhibited canonical Wnt/β-catenin pathway, observing a loss of nuclear β-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3β and an increase of phosphorylated β-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3β, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3β and β-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed.Our results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/β-catenin pathway through the increase of Gsk3β expression and β-catenin phosphorylation.http://europepmc.org/articles/PMC4892678?pdf=render |
| spellingShingle | Carmen Herencia Juan Miguel Diaz-Tocados Lidia Jurado Addy Montes de Oca Maria Encarnación Rodríguez-Ortiz Carmen Martín-Alonso Julio M Martínez-Moreno Noemi Vergara Mariano Rodríguez Yolanda Almadén Juan R Muñoz-Castañeda Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. PLoS ONE |
| title | Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. |
| title_full | Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. |
| title_fullStr | Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. |
| title_full_unstemmed | Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. |
| title_short | Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. |
| title_sort | procaine inhibits osteo odontogenesis through wnt β catenin inactivation |
| url | http://europepmc.org/articles/PMC4892678?pdf=render |
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