Document Detail


β-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice.
MedLine Citation:
PMID:  23188722     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jianquan Chen; Fanxin Long
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  28     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-18     Completed Date:  2013-10-18     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1160-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Society for Bone and Mineral Research.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Bone Development / physiology*
Bone Diseases, Metabolic / physiopathology
Bone Resorption*
Cell Lineage
DNA Primers
Mice
Osteoblasts / cytology*
Polymerase Chain Reaction
beta Catenin / physiology*
Grant Support
ID/Acronym/Agency:
AR055923/AR/NIAMS NIH HHS; AR060456/AR/NIAMS NIH HHS; P30 AR057235/AR/NIAMS NIH HHS; P30 AR057235/AR/NIAMS NIH HHS; R01 AR055923/AR/NIAMS NIH HHS; R01 AR060456/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/beta Catenin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  SATB1 expression in gastric mucosa in relation to Helicobacter pylori infection and family history o...
Next Document:  Retinal Vascular Rescue of Oxygen Induced Retinopathy in Mice by Norrin.