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PTHrP increases RANKL expression by stromal cells from giant cell tumor of bone.
MedLine Citation:
PMID:  22102368     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Giant cell tumor of bone (GCT) presents with numerous osteoclast-like multinucleated giant cells that are principally responsible for the extensive bone resorption by the tumor. Although the precise etiology of GCT remains uncertain, the accumulation of giant cells is partially due to the high expression of the receptor activator of nuclear factor-κB ligand (RANKL) from the neoplastic stromal cells. Here, we have investigated whether parathyroid hormone-related protein (PTHrP) plays a role in the pathogenesis of GCT. Immunohistochemistry results revealed PTHrP expression in the stromal cells of the tumor, and that its receptor, the parathyroid hormone type 1 receptor (PTH1R), is expressed by both the stromal cells and giant cells. PCR and Western blot analyses confirmed the expression of PTHrP and PTH1R by isolated stromal cells from five patients presenting with GCT. Treatment of GCT stromal cells with varying concentrations of PTHrP (1-34) significantly increased both RANKL gene expression and the number of multinucleated cells formed from RAW 264.7 cells in co-culture experiments, whereas inhibition of PTHrP with a neutralizing antibody decreased RANKL gene expression. These results suggest that PTHrP is expressed within GCT by the stromal cells and can contribute to the abundant RANKL expression and giant cell formation within the tumor. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Authors:
Robert W Cowan; Gurmit Singh; Michelle Ghert
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-18
Journal Detail:
Title:  Journal of orthopaedic research : official publication of the Orthopaedic Research Society     Volume:  -     ISSN:  1554-527X     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8404726     Medline TA:  J Orthop Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Orthopaedic Research Society.
Affiliation:
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Juravinski Cancer Centre, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2.
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