| First Author | Chen J | Year | 2013 |
| Journal | J Bone Miner Res | Volume | 28 |
| Issue | 5 | Pages | 1160-9 |
| PubMed ID | 23188722 | Mgi Jnum | J:313136 |
| Mgi Id | MGI:6791182 | Doi | 10.1002/jbmr.1834 |
| Citation | Chen J, et al. (2013) beta-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice. J Bone Miner Res 28(5):1160-9 |
| abstractText | Genetic studies in the mouse have demonstrated multiple roles for beta-catenin in the skeleton. In the embryo, beta-catenin is critical for the early stages of osteoblast differentiation. Postnatally, beta-catenin in mature osteoblasts and osteocytes indirectly suppresses osteoclast differentiation. However, a direct role for beta-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 beta-catenin, controls osteoblast number and function in postnatal mice or humans. To overcome the neonatal lethality caused by embryonic deletion of beta-catenin in early-stage osteoblast-lineage cells, we use the Osx-CreER(T2) mouse strain to remove beta-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 beta-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, beta-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. |
