Document Detail


Gpr177, a novel locus for bone mineral density and osteoporosis, regulates osteogenesis and chondrogenesis in skeletal development.
MedLine Citation:
PMID:  23188710     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human genetic analysis has recently identified Gpr177 as a susceptibility locus for bone mineral density and osteoporosis. Determining the unknown function of this gene is therefore extremely important to furthering our knowledge base of skeletal development and disease. The protein encoded by Gpr177 exhibits an ability to modulate the trafficking of Wnt, similar to the Drosophila Wls/Evi/Srt. Because it plays a critical role in Wnt regulation, Gpr177 might be required for several key steps of skeletogenesis. To overcome the early lethality associated with the inactivation of Gpr177 in mice, conditional gene deletion is used to assess its functionality. Here we report the generation of four different mouse models with Gpr177 deficiency in various skeletogenic cell types. The loss of Gpr177 severely impairs development of the craniofacial and body skeletons, demonstrating its requirement for intramembranous and endochondral ossifications, respectively. Defects in the expansion of skeletal precursors and their differentiation into osteoblasts and chondrocytes suggest that Wnt production and signaling mediated by Gpr177 cannot be substituted. Because the Gpr177 ablation impairs Wnt secretion, we therefore identify the sources of Wnt proteins essential for osteogenesis and chondrogenesis. The intercross of Wnt signaling between distinct cell types is carefully orchestrated and necessary for skeletogenesis. Our findings lead to a proposed mechanism by which Gpr177 controls skeletal development through modulation of autocrine and paracrine Wnt signals in a lineage-specific fashion.
Authors:
Takamitsu Maruyama; Ming Jiang; Wei Hsu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
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:  1150-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Society for Bone and Mineral Research.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Density / genetics*
Bone Development / genetics*
Intracellular Signaling Peptides and Proteins / genetics*
Mice
Osteoblasts / cytology
Osteoporosis / genetics*
Receptors, G-Protein-Coupled / genetics*
Signal Transduction
Wnt Proteins / metabolism
Grant Support
ID/Acronym/Agency:
DE015654/DE/NIDCR NIH HHS; R01 DE015654/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Gpr177 protein, mouse; 0/Intracellular Signaling Peptides and Proteins; 0/Receptors, G-Protein-Coupled; 0/Wnt Proteins
Comments/Corrections

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