Crucial roles of canonical Runx2-dependent pathway on Wnt1-induced osteoblastic differentiation of human periodontal ligament fibroblasts.

Crucial roles of canonical Runx2-dependent pathway on Wnt1-induced osteoblastic differentiation of human periodontal ligament fibroblasts. Mol Cell Biochem. 2015 Jan 25; Authors: Kook SH, Heo JS, Lee JC Abstract Canonical Wnt signaling is thought to enhance osteogenic differentiation of human periodontal ligament fibroblasts (hPLFs). However, the mechanism of this enhancement has not yet been defined. We investigated the effects of Wnt1 on osteoblast differentiation of hPLFs and explored the mechanisms of the effects. Treating hPLFs with Wnt1 induced cytosolic accumulation and nuclear translocation of β-catenin with concomitant increases in alkaline phosphatase (ALP) activity and calcium content in a time-dependent and dose-dependent manner. Wnt1-stimulated differentiation of hPLFs was accompanied by augmented phosphorylation of glycogen synthase kinase (GSK)-3β and expression of the bone-specific factors runt-related transcription factor 2 (Runx2), osterix2 (Osx2), ALP, type I collagen, osteopontin, and osteocalcin. Pretreatment with Dickkopf-1 inhibited Wnt1-stimulated differentiation of hPLFs by suppressing GSK-3β phosphorylation, nuclear translocation of β-catenin, and expression of the bone-specific factors. Small interfering (si) RNA-mediated knockdown of β-catenin, or pretreatment with FH535, markedly prevented Wnt1-stimulated differentiation of cells by blocking Runx2 and its downstream factors at the mRNA and protein le...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research