β-catenin-dependent High Bone Mass Induced by Loss of APC in Osteoblasts Does Not Require Lrp5 or Lrp6.

The requirement for LRP5 and LRP6 to prevent β-catenin degradation in the absence of the tumor suppressor APC is unclear because cell culture models have yielded conflicting results. We previously established that osteoblast-specific loss of APC causes β-catenin accumulation and increased bone mass, while loss of both LRP5 and LRP6 reduces bone mass. We report here that the simultaneous loss of APC, LRP5, and LRP6 in osteoblasts in mice phenocopies the APC osteoblast-specific knockout. Thus, β-catenin stabilization and increased bone mass after loss of APC in osteoblasts in vivo are not dependent on LRP5 and LRP6.