The canonical Wnt signalling pathway, which has an important role in bone formation, is negatively regulated by Axin1 and its homologue Axin2 through their capacity to degrade β-catenin. Previous work has shown that Axin1 and Axin2 have distinct but overlapping functions: deletion of Axin1 is embryonic lethal in mice, whereas deletion of Axin2 has less marked effects. On , Di Chen and colleagues investigate the unique role of Axin2 in bone remodelling in a study of Axin2-deficient mice. Their analyses show that, compared with wild-type mice, Axin2-deficient adult mice have greater bone mass and a higher rate of bone formation. The authors show that this is due to an increase in the proliferation and differentiation of osteoblasts (which build bone) as well as a decrease in the formation and function of osteoclasts (which resorb bone). Because most of the alterations in Axin2-deficient cells are rescued in the absence of β-catenin expression, the authors conclude that β-catenin activation underlies the increase in osteoblast function and bone formation observed in Axin2-deficient mice. Finally, the authors provide additional evidence that bone remodelling involves crosstalk between Axin2–β-catenin signalling and the bone-morphogenetic-protein pathway. These data increase our understanding of bone remodelling at the molecular level, which is relevant for managing and treating osteoporosis.
