Runx2 Controls Bone Resorption through the Down-regulation of the Wnt Pathway in Osteoblasts.

Runx2 Controls Bone Resorption through the Down-regulation of the Wnt Pathway in Osteoblasts.
Am J Pathol. 2016 Apr 12;
Authors: Haxaire C, Haÿ E, Geoffroy V
Abstract
The transcription factor Runx2 and the Wnt/β-catenin pathway are major regulators of bone formation. Our aim was to assess the potential interactions between the Wnt/β-catenin pathway and Runx2 that contribute to bone resorption. Our results indicate that the activity of the canonical Wnt/β-catenin pathway depends on Runx2. Runx2 overexpression inhibited β-catenin levels and activity in vitro and in vivo. Inhibition of Gsk3b using lithium chloride in Runx2-overexpressing osteoporotic female mice rescued the Wnt/β-catenin signaling in vivo and completely restored trabecular bone volume by increasing bone formation and decreasing bone resorption. The activation of Wnt/β-catenin signaling by lithium chloride treatment reduced the number and activity of bone marrow-derived osteoclast-like cells in vitro, suggesting that the restoration of trabecular bone in vivo was due to decreased bone resorption, consistent with the reduced receptor activator of NF-κB ligand/osteoprotegerine ratio in Runx2-overexpressing osteoblasts. Lithium chloride also increased osteoblast differentiation and activity in vitro in agreement with the increase in mineral apposition rate and osteocalcin expression detected in vivo. Our results indicate that the activity of the canonical W...

Source: The American Journal of Pathology - April 11, 2016 Category: Pathology Authors: Haxaire C, Haÿ E, Geoffroy V Tags: Am J Pathol Source Type: research