β‐catenin promotes bone formation and suppresses bone resorption in postnatal growing mice

摘要: Genetic studies in the mouse have demonstrated multiple roles for β-catenin skeleton. In embryo, is critical early stages of osteoblast differentiation. Postnatally, mature osteoblasts and osteocytes indirectly suppresses osteoclast However, a direct role regulating number and/or function specifically postnatal life has not been demonstrated. Addressing this knowledge gap important because low-density lipoprotein receptor-related protein 5 (LRP5), coreceptor WNT signaling proposed to through β-catenin, controls mice or humans. To overcome neonatal lethality caused by embryonic deletion early-stage osteoblast-lineage cells, we use Osx-CreER(T2) strain remove Osterix (Osx)-expressing cells administering tamoxifen (TM) temporarily mice. Lineage-tracing experiments long bones demonstrate that targets predominantly on bone surface, but also transient progenitors contribute marrow stromal adipocytes. Deletion strategy greatly reduces formation activity targeted osteoblasts. rapidly turn over are replaced an excessive non-targeted osteoblasts, causing unexpected increase formation, even greater produces net effect severe osteopenia. With time, mutant exhibit marked adiposity. Thus, Osx-lineage critically regulates homeostasis promoting suppressing turnover, while restraining fat formation.