RT Journal Article
T1 Procaine Inhibits Osteo/Odontogenesis through Wnt/beta-Catenin Inactivation
A1 Herencia, Carmen
A1 Miguel Diaz-Tocados, Juan
A1 Jurado, Lidia
A1 Montes de Oca, Addy
A1 Encarnacion Rodriguez-Ortiz, Maria
A1 Martin-Alonso, Carmen
A1 Martinez-Moreno, Julio M.
A1 Vergara, Noemi
A1 Rodriguez, Mariano
A1 Almaden, Yolanda
A1 Munoz-Castaneda, Juan R.
K1 Differentiation
K1 Sclerostin
K1 Periodontitis
AB IntroductionPeriodontitis 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.MethodsIn 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.ResultsProcaine 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/beta-catenin pathway, observing a loss of nuclear beta-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3 beta and an increase of phosphorylated beta-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3 beta, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3 beta and beta-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed.ConclusionsOur results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/beta-catenin pathway through the increase of Gsk3 beta expression and beta-catenin phosphorylation.
PB Public library science
SN 1932-6203
YR 2016
FD 2016-06-03
LK http://hdl.handle.net/10668/19148
UL http://hdl.handle.net/10668/19148
LA en
DS RISalud
RD Apr 8, 2025