The effects of Dickkopf-4 on the proliferation, differentiation, and apoptosis of osteoblasts.

The effects of Dickkopf-4 on the proliferation, differentiation, and apoptosis of osteoblasts.
Endocrinology. 2013 Oct 8;
Authors: Hiramitsu S, Terauchi M, Kubota T
Abstract
The Dickkopf family of proteins is comprised of four members (Dkk1, 2, 3, 4) that are known to modulate Wnt/β-catenin signaling, which is activated during bone formation. Although the effects of Dkk1 on Wnt/β-catenin signaling have been well studied, little is known about the effects of Dkk4. Therefore, to evaluate the role of Dkk4 in osteoblastogenesis, we used the mouse osteoblastic cell line MC3T3-E1, in which Dkk4 expression was suppressed by siRNA knockdown. Our results showed that suppression of Dkk4 expression promoted osteoblast proliferation and differentiation, and suppressed apoptosis. In colony-forming unit alkaline phosphatase (CFU-ALP) assay, Dkk4 knockdown cells possessed markedly higher ALP activity compared with Dkk1 knockdown cells. Reduced Dkk4 expression also led to upregulation of β-catenin levels, β-catenin/T cell factor (TCF) activity, and Wnt-target genes. In contrast, overexpression of Dkk4 in MC3T3-E1 cells led to inhibition of osteoblast differentiation. Our findings reveal that Dkk4 functions as an inhibitor of osteoblastogenesis through Wnt/β-catenin signaling, providing new insights into the relationship between Wnt/β-catenin signaling and Dkk4 in bone formation.
PMID: 24105477 [PubMed - as supplied by publisher]

Source: Endocrinology - October 8, 2013 Category: Endocrinology Authors: Hiramitsu S, Terauchi M, Kubota T Tags: Endocrinology Source Type: research