RT Journal Article
T1 Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation.
A1 Herencia, Carmen
A1 Diaz-Tocados, Juan Miguel
A1 Jurado, Lidia
A1 Montes de Oca, Addy
A1 Rodriguez-Ortiz, Maria Encarnacion
A1 Martín-Alonso, Carmen
A1 Martinez-Moreno, Julio M
A1 Vergara, Noemi
A1 Rodriguez, Mariano
A1 Almaden, Yolanda
A1 Muñoz-Castañeda, Juan R
K1 Animals
K1 Calcium
K1 Cell differentiation
K1 Cell proliferation
K1 Cells, cultured
K1 DNA methylation
AB 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.
PB Public Library of Science
YR 2016
FD 2016-05-19
LK http://hdl.handle.net/10668/10150
UL http://hdl.handle.net/10668/10150
LA en
NO Herencia C, Diaz-Tocados JM, Jurado L, Montes de Oca A, Rodríguez-Ortiz ME, Martín-Alonso C, et al. Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. PLoS One. 2016 Jun 3;11(6):e0156788
DS RISalud
RD Apr 7, 2025