Axin2 Controls Bone Remodeling through β-Catenin-BMP Signaling Pathway in Adult Mice

INTRODUCTION: Bone remodeling, a dynamic process involving bone resorption followed by bone formation, takes place throughout life to maintain bone homeostasis. Osteoporosis pseudoglioma (OPPG) syndrome and high bone mass (HBM) syndrome are both mapped to the locus of Lrp5, a receptor for Wnt ligands in activation of β-catenin signaling (1). OPPG patients harbor inactivating mutations in the Lrp5 gene (2). In contrast, an activating mutation (Gly171Val) in Lrp5 is responsible for the HBM syndrome (3). These findings clearly link Wnt/β-catenin signaling through LRP5 to the regulation of bone mass. Axin2 is a protein scaffold shown to mediate APC-induced β-catenin degradation, thereby, acting as a negative regulator of β-catenin signaling (4). We analyzed the bone phenotype of adult female Axin2-lacZ knockout (KO) mice (5) in order to investigate the mechanism by which Wnt/β-catenin signaling regulates bone remodeling.