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Plos One : Targeting the Giant Cell Tumor Stromal Cell ; Functional Characterization and a Novel Therapeutic Strategy, Volume 8

By Rameshwar, Pranela

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Book Id: WPLBN0003967498
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Targeting the Giant Cell Tumor Stromal Cell ; Functional Characterization and a Novel Therapeutic Strategy, Volume 8  
Author: Rameshwar, Pranela
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
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Publisher: Plos

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Rameshwar, P. (n.d.). Plos One : Targeting the Giant Cell Tumor Stromal Cell ; Functional Characterization and a Novel Therapeutic Strategy, Volume 8. Retrieved from http://netlibrary.net/


Description
Description : Giant cell tumor of bone (GCTB) is a benign, locally destructive neoplasm, with tumors comprised of mesenchymal fibroblast-like stromal cells: monocytic, mononuclear cells of myeloid lineage: and the characteristic osteoclast-like, multinucleated giant cells. Hampering the study of the complex interaction of its constituent cell types is the propensity of longstanding, repeatedly passaged cell cultures to undergo phenotypic alteration and loss of osteoclastinducing capacities. In this study, we employed a novel, single-step technique to purify freshly harvested stromal cells using a CD14-negative selection column. Using 9 freshly harvested GCTB specimens and the purified stromal cell component, we performed analyses for markers of osteoblast lineage and analyzed the capacity of the stromal cells to undergo osteoblastic differentiation and induce osteoclastogenesis in co-cultures with monocytic cells. Successful purification of the CD14-negative stromal cells was confirmed via flow cytometric analysis and immunocytochemistry. Osteogenic media upregulated the expression of osteocalcin, suggesting an osteoblastic lineage of the GCTB stromal cells. The effects of the Wnt pathway agonist, SB415286, and recombinant human bone morphogenetic protein (BMP)-2 on osteoblastogenesis varied among samples. Notably, osteogenic media and SB415286 reversed the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) expression ratio resulting in diminished osteoclastogenic capacity. Recombinant human BMP2 had the opposite effect, resulting in enhanced and sustained support of osteoclastogenesis. Targeting the giant cell tumor stromal cell may be an effective adjunct to existing antiresorptive strategies.

 

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