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

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/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. PLO

Historia y fundamentos epistemológicos de la línea de pedagogía, Maestría en Educación, Universidad Santo Tomás

El presente artículo de investigación es un producto de reflexión resultado del trabajo colectivo de los miembros de la Línea de Pedagogía de la Maestría en Educación de la Universidad Santo Tomás. Se genera un proceso que intente recoger la historia de la Línea de Pedagogía, junto con el fundamento epistemológico de los ejes de investigación que permean la línea, como lo son, la filosofía tomista, la didáctica, el currículo y la evaluación. El objetivo de este trabajo es resaltar la intención fundante de la Maestría en Educación, basada en la formación de magister investigadores con competencias integradoras que reflexionen y orienten la producción del conocimiento científico en el campo pedagógico-educativo. Asimismo, la Línea de Pedagogía, está orientada a reflexionar, discutir y profundizar, sobre el pensamiento pedagógico dominicano-tomista, pedagogías contemporáneas y emergentes, pensamiento pedagógico latinoamericano, investigación curricular, prácticas pedagógicas, evaluación y didáctica

Search for low-mass WIMPs in a 0.6 kg day exposure of the DAMIC experiment at SNOLAB

We present results of a dark matter search performed with a 0.6 kg day exposure of the DAMIC experiment at the SNOLAB underground laboratory. We measure the energy spectrum of ionization events in the bulk silicon of charge-coupled devices down to a signal of 60 eV electron equivalent. The data are consistent with radiogenic backgrounds, and constraints on the spin-independent WIMP-nucleon elastic-scattering cross section are accordingly placed. A region of parameter space relevant to the potential signal from the CDMS-II Si experiment is excluded using the same target for the first time. This result obtained with a limited exposure demonstrates the potential to explore the low-mass WIMP region (<10 GeV/$c^{2}$) of the upcoming DAMIC100, a 100 g detector currently being installed in SNOLAB.Comment: 11 pages, 11 figure

Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSC) are osteoblasts progenitors and a variety of studies suggest that they may play an important role for the health in the field of bone regeneration. Magnesium supplementation is gaining importance as adjuvant treatment to improve osteogenesis, although the mechanisms involving this process are not well understood. The objective of this study was to investigate the effects of magnesium on MSC differentiation. Here we show that in rat bone marrow MSC, magnesium chloride increases MSC proliferation in a dose-dependent manner promoting osteogenic differentiation and mineralization. These effects are reduced by 2-APB administration, an inhibitor of magnesium channel TRPM7. Of note, magnesium supplementation did not increase the canonical Wnt/β-catenin pathway, although it promoted the activation of Notch1 signaling, which was also decreased by addition of 2-APB. Electron microscopy showed higher proliferation, organization and maturation of osteoblasts in bone decellularized scaffolds after magnesium addition. In summary, our results demonstrate that magnesium chloride enhances MSC proliferation by Notch1 signaling activation and induces osteogenic differentiation, shedding light on the understanding of the role of magnesium during bone regeneration

First Direct-Detection Constraints on eV-Scale Hidden-Photon Dark Matter with DAMIC at SNOLAB

We present direct detection constraints on the absorption of hidden-photon dark matter with particle masses in the range $1.2–30  eV c^{−2}$ with the DAMIC experiment at SNOLAB. Under the assumption that the local dark matter is entirely constituted of hidden photons, the sensitivity to the kinetic mixing parameter κ is competitive with constraints from solar emission, reaching a minimum value of $2.2 \times 10^{−14}$ at $17  eV c^{−2}$. These results are the most stringent direct detection constraints on hidden-photon dark matter in the galactic halo with masses $3–12  eV c^{−2}$ and the first demonstration of direct experimental sensitivity to ionization signals $< 12  eV$ from dark matter interactions

Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration.

Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) in vitro and in vivo. To create a PTH "clamp," total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH. Animals were then treated with either the calcimimetic or vehicle. Calcimimetic administration increased osteoblast number and osteoid volume in normal rats under a PTH clamp. In uremic rats, the elevated PTH concentration led to reduced bone volume and increased bone turnover, and calcimimetic administration decreased plasma PTH. In uremic rats exposed to PTH at 6-fold the usual replacement dose, calcimimetic administration increased osteoblast number, osteoid surface, and bone formation. A 9-fold higher dose of PTH caused an increase in bone turnover that was not altered by the administration of calcimimetic. In an osteosarcoma cell line, the calcimimetic induced Erk1/2 phosphorylation and the expression of osteoblast genes. The addition of a calcilytic resulted in the opposite effect. Moreover, the calcimimetic promoted the osteogenic differentiation and mineralization of human bone marrow mesenchymal stem cells in vitro. Thus, calcimimetic administration has a direct anabolic effect on bone that counteracts the decrease in PTH levels