Dataset Information

Procaine Inhibits Osteo/Odontogenesis through Wnt/?-Catenin Inactivation.

ABSTRACT:

Introduction

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.

Methods

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.

Results

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/?-catenin pathway, observing a loss of nuclear ?-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3? and an increase of phosphorylated ?-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3?, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3? and ?-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed.

Conclusions

Our results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/?-catenin pathway through the increase of Gsk3? expression and ?-catenin phosphorylation.

SUBMITTER: Herencia C

PROVIDER: S-EPMC4892678 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation.

Herencia Carmen C Diaz-Tocados Juan Miguel JM Jurado Lidia L Montes de Oca Addy A Rodríguez-Ortiz Maria Encarnación ME Martín-Alonso Carmen C Martínez-Moreno Julio M JM Vergara Noemi N Rodríguez Mariano M Almadén Yolanda Y Muñoz-Castañeda Juan R JR

PloS one 20160603 6

<h4>Introduction</h4>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 d ...[more]

PMID: 27257912

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