The production is involved in the stabilization of the entire B-catenin. Whether the mechanical load induced upregulation of a total of b catenin and activation NVP-BEP800 VER-82576 of the sequence b catenin mediated by PI3K/Akt is MLO Y4 osteocytes were to 30 min PFF treatment in the presence of LY 294002 PI3K inhibitor subjected. In MLO Y4 osteocytes, increases ht PFF 30 min treatment levels of phosphorylated Akt relative to static control cultures, but treatment with LY 294002 before for 1 h before the treatment, the PFF PFF raises induced effect on the phosphorylation act Pretreatment of osteocytes for 1 h with LY 294002 by 30 minutes of static incubation was followed by no influence on the total concentration of b catenin, but LY 294002 reduced the PFF-induced upregulation of a total of b catenin by 1.
7 times. Three thirty minutes to PFF target genes regulated CD44, connexin 43, cyclin D1, c-fos and c of 1.7, 3.2, 2.4 and 1.9 times, respectively. gsk3 beta Pretreatment with LY 294002 abolished the PFF-induced upregulation of CD44, connexin 43, cyclin D1 and c-fos, indicating that PI3K/Akt is involved in stabilizing b catenin pathway activation and b catenin in response to PFF. To determine whether the Changes induced PFF total of b catenin and the consequent activation of b-catenin path through activation of the PI3K/Akt path Fak, were MLO Y4 osteocytes to 30 min in the presence of PFF exposed FAK inhibitor 14th Pretreatment of MLO Y4 osteocytes with an inhibitor of FAK 14 for 1 h before the experiments PFF managed, the effect of PFF induced Akt.
Pretreatment of MLO Y4 osteocytes with an inhibitor of FAK 14 for 1 h, followed by 30 minutes static incubation had no effect on the total concentration of b catenin, but FAK inhibitor 14 reduces upregulation PFF-induced total of b catenin by the 2,6 -fold. Pretreatment of osteocytes for 1 h with an inhibitor of FAK 14 min followed by 30 to PFF-regulated gene expression of CD44 by 1.3-fold, but has no effect on connexin 43, the cyclin D1 gene and expression of the c- fos. Pre-treatment with inhibitors of FAK abolished the 14 PFF induced upregulation of CD44, connexin 43, cyclin D1 and c-fos, suggesting that FAK b catenin stabilization and activation f Promoted in b catenin response to PFF through the activation of PI3K / Akt path.
Discussion activation of the Wnt / b catenin was shown that the adaptive for the reaction of the bone to mechanical stress, but the r The activation of this pathway osteocytes w During mechanical stimulation of n ‘is not completely Ndig understood. We and others have shown that mechanical loading b catenin stabilization and translocation into the nucleus bcatenin followed, and the expression of target genes b catenin, such as CD44, connexin 43, cyclin D1, c-fos and c induced. Mechanical stress activated immediately, b-catenin-independent Ngigen Wnt production and a sp Later time it is activated by Wnt-b catenin stimulation of the expression. In this study we have tried to understand what upstream events that led to stabilization of the b catenin independent of mechanical stress Ngig of Wnt production in osteocytes. First, we have shown that the mechanical loading by PFF effectively results in the stabilization of the b catenin and activation of the b catenin signaling in osteocytes. We used the well-founded