Document Detail

Ift88 regulates Hedgehog signaling, Sfrp5 expression, and β-catenin activity in post-natal growth plate.
MedLine Citation:
PMID:  23034798     Owner:  NLM     Status:  MEDLINE    
Primary cilia are present on most cell types including chondrocytes. Dysfunction of primary cilia results in pleiotropic symptoms including skeletal dysplasia. Previously, we showed that deletion of Ift88 and subsequent depletion of primary cilia from chondrocytes resulted in disorganized columnar structure and early loss of growth plate. To understand underlying mechanisms whereby Ift88 regulates growth plate function, we compared gene expression profiles in normal and Ift88 deleted growth plates. Pathway analysis indicated that Hedgehog (Hh) signaling was the most affected pathway in mutant growth plate. Expression of the Wnt antagonist, Sfrp5, was also down-regulated. In addition, Sfrp5 was up-regulated by Shh in rib chondrocytes and regulation of Sfrp5 by Shh was attenuated in mutant cells. This result suggests Sfrp5 is a downstream target of Hh and that Ift88 regulates its expression. Sfrp5 is an extracellular antagonist of Wnt signaling. We observed an increase in Wnt/β-catenin signaling specifically in flat columnar cells of the growth plate in Ift88 mutant mice as measured by increased expression of Axin2 and Lef1 as well as increased nuclear localization of β-catenin. We propose that Ift88 and primary cilia regulate expression of Sfrp5 and Wnt signaling pathways in growth plate via regulation of Ihh signaling.
Ching-Fang Chang; Rosa Serra
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-03
Journal Detail:
Title:  Journal of orthopaedic research : official publication of the Orthopaedic Research Society     Volume:  31     ISSN:  1554-527X     ISO Abbreviation:  J. Orthop. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-03-26     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  8404726     Medline TA:  J Orthop Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  350-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Orthopaedic Research Society.
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MeSH Terms
Cells, Cultured
Chondrocytes / cytology,  metabolism*
Cilia / metabolism
Down-Regulation / genetics
Growth Plate / cytology,  metabolism*
Hedgehog Proteins / metabolism*
Intercellular Signaling Peptides and Proteins / metabolism*
Mice, Mutant Strains
Ribs / cytology,  growth & development,  physiology
Transcriptome / physiology
Tumor Suppressor Proteins / genetics,  metabolism*
Up-Regulation / genetics
Wnt Signaling Pathway / physiology
beta Catenin / metabolism*
Grant Support
Reg. No./Substance:
0/Catnb protein, mouse; 0/Hedgehog Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Sfrp5 protein, mouse; 0/Shh protein, mouse; 0/Tg737Rpw protein, mouse; 0/Tumor Suppressor Proteins; 0/beta Catenin

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

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