MLO Y4 osteocyte cell line, and b catenin as an indication of increased total Hte stabilizing b catenin SB939 and measured gene expression of target genes b catenin as an indicator of activation of the pathway bcatenin. We found that the treatment min briefly of 30 PFF to a recd Hung of the total-concentration of from b catenin, and upregulation of CD44-target genes, Connexin 43, Cyclin D1, c-fos and PFF indicating that led to, activation of B-catenin in MLO Y4 osteocytes. Our results are consistent with previously reported observations indicate that treatment of the shear stress results MLO nucleic Y4 osteocytes in b catenin Translocation and re Ver Changes in the expression of b catenin target genes. We have reported tt, that activation of the pathway is performed by PFF bcatenin Wnt-induced production Haupts Chlich at 1 3 h after cessation of therapy in 1 hour PFF MLOY4 osteocytes.
Therefore, the b catenin stabilization was observed immediately after completion of treatment 30 min PFF probably occurred independently Ngig of the Wnt receptor binding LRP5 / 6 Our results are consistent with other studies, the osteoblast cell line pre-MMIC 4, showing that treatment with the antagonist before Dickopf Wnt-1 to disrupt Wnt signaling pathway by binding to the atm cancer Wnt receptor LRP5, does not prevent stress- induced nucleotide re translocation of b catenin and up regulation of b catenin target genes WISP 2 and COX-2. This suggests that mechanical stimuli directly affected b catenin without the involvement of Wnt molecules. It has been suggested that each channel, the active act k Nnte lead to a stabilization of b-catenin phosphorylation by GSK 3b.
Therefore, we focused on molecules that are involved in the bone response to mechanical stress and lead m for may have a stabilizing b catenin, the hot t NO, PI3K, and FAK. We showed for the first time that the inhibition of NO production PFF with results THE NAME in the inhibition the PFF induced-stabilization of the b catenin induced. N is produced when L is converted to arginine L citrulline, together in the presence of nitric oxide synthase enzyme, molecular oxygen, NADPH and other factors. The mechanism may be provided through the NO b catenin stabilization is unknown, but anything similar observations were reported by others, that is not derived from inducible NO synthase positively correlated with the regulation of WISP b catenin target gene in cancer cell lines.
In addition, due to the NO donor DETA NONOate students WISP 1 mRNA and protein expression independently Ngig dependent on catenin from Independent, but in human colon epithelial Wnt, an r Top to NO in the stabilization of the b catenin. Our observations have not Aufschlu about the exact mechanism, through the NO-production leads to b catenin-stabilization, this further investigation PFF induces-. We found that the inhibition of PI3K with LY 294002 in inhibition of PFF-induced stabilization of b catenin and PFF-induced activation of the b catenin in MLO Y4 osteocytes. This indicates that PI3K is involved in the signaling pathway that leads to the stabilization of b catenin in osteocytes in response to PFF. PI3K is required for activation by fluid shear act stressstimulated Akt phosphorylation and activation of pathways downstream Rts of Akt signaling