title: β-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice.
abstract: Genetic studies in the mouse have demonstrated multiple roles for β-catenin in the skeleton. In the embryo, β-catenin is critical for the early stages of osteoblast differentiation. Postnatally, β-catenin in mature osteoblasts and osteocytes indirectly suppresses osteoclast differentiation. However, a direct role for β-catenin in regulating osteoblast number and/or function specifically in the postnatal life has not been demonstrated. Addressing this knowledge gap is important because low-density lipoprotein receptor-related protein 5 (LRP5), a coreceptor for WNT signaling proposed to function through β-catenin, controls osteoblast number and function in postnatal mice or humans. To overcome the neonatal lethality caused by embryonic deletion of β-catenin in early-stage osteoblast-lineage cells, we use the Osx-CreER(T2) mouse strain to remove β-catenin in Osterix (Osx)-expressing cells by administering tamoxifen (TM) temporarily to postnatal mice. Lineage-tracing experiments in the long bones demonstrate that Osx-CreER(T2) targets predominantly osteoblast-lineage cells on the bone surface, but also transient progenitors that contribute to bone marrow stromal cells and adipocytes. Deletion of β-catenin by this strategy greatly reduces the bone formation activity of the targeted osteoblasts. However, the targeted osteoblasts rapidly turn over and are replaced by an excessive number of non-targeted osteoblasts, causing an unexpected increase in bone formation, but an even greater increase in osteoclast number and activity produces a net effect of severe osteopenia. With time, the mutant mice also exhibit a marked increase in bone marrow adiposity. Thus, β-catenin in postnatal Osx-lineage cells critically regulates bone homeostasis by promoting osteoblast activity and suppressing osteoblast turnover, while restraining osteoclast and marrow fat formation.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63131, USA.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Chen
authors.forename: Fanxin
authors.initials: F
authors.lastname: Long
mesh_terms: D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000503:physiopathology; D001862:Bone Resorption; D019070:Cell Lineage; D017931:DNA Primers; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D016133:Polymerase Chain Reaction; D051176:beta Catenin / Q000502:physiology*
chemical_list: D017931:DNA Primers; D051176:beta Catenin