Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts.

Ghrelin, by binding growth hormone secretagogue receptor (GHS-R), promotes osteoblast proliferation but the signaling mechanism of GHS-R on these cells remains unclear. Since canonical Wnt/β-catenin pathway is critically associated with bone homeostasis, we investigated its involvement in mediating ghrelin effects in osteoblasts and in osteoblast-osteoclast cross talk. Ghrelin (10(-10)M) significantly increased β-catenin levels in rat osteoblasts (rOB). This stimulatory action on β-catenin involves a specific interaction with GHS-R1a, as it is prevented by the selective GHS-R1a antagonist, D-Lys(3)-GHRP-6 (10(-7)M). The effect of ghrelin on β-catenin involves the phosphorylation and inactivation of GSK-3β via protein kinase A (PKA). Inhibition of PKA activity reduces the facilitatory action of ghrelin on β-catenin stabilization. Ghrelin treatment of rOB significantly increases the expression of osteoprotegerin (OPG), which plays an important role in the regulation of osteoclastogenesis, and this effect is blocked by D-Lys(3)-GHRP-6. Furthermore, ghrelin reduced RANKL/OPG ratio thus contrasting osteoclastogenesis. Accordingly, conditioned media from rOB treated with ghrelin decreased the number of multinucleated TRAcP+ cells as compared with the conditioned media from untreated-control rOB. Our data suggest new roles for ghrelin in modulating bone homeostasis via a specific interaction with GHSR-1a in osteoblasts with subsequent enhancement of both β-catenin levels and OPG expression

Analysis of RWM with a 3D Model of Conducting Structures

Abstract In this paper we present some preliminary results of a coupling between the MHD stability code MARS-F and the three-dimensional eddy currents code CARIDDI, aimed at the analysis of Resistive Wall Modes with 3D conducting structures

Strontium absorption and excretion in normocalciuric subjects : relation to calcium metabolism

The relationships of Sr intestinal absorption and renal excretion with biohumoral factors regulating Ca metabolism were studied in 47 normocalciuric subjects with Ca kidney stones. Sr concentrations were measured in serum and urine after an oral load of stable Sr (30.2 mumol/kg body wt). Enteral absorption of the ion (9.77 +/- 0.438 mmol.L-1.min, 240 min after Sr administration), expressed as the area under the plasma concentration-time curve (AUC), and renal clearance (CRE) in these subjects during the test (2.80 +/- 0.336 mL/min) were not different from values for 27 controls. CRE was not correlated with AUCs. Plasma concentrations of parathyroid hormone (PTH) negatively correlated with AUCs (P < 0.01) and correlated with CRE after one outlier was excluded (P < 0.05). Plasma concentrations of 1,25-dihydroxyvitamin D correlated positively with AUCs (P < 0.01) when normalized to the plasma concentration of PTH. Multiple stepwise regression showed that PTH and phosphatemia were significantly related to AUC values at 240 min (P < 0.01). These findings suggest that Sr absorption and excretion reflect the regulation of Ca metabolism, but some differences in renal handling of the two ions may exist