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Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

ABSTRACT: Purpose: We have used microarrays to identify gene expression profiles that distinguish mouse OS cells from normal pre-osteoblast cells and mature osteoblast cells. Methods: Transcriptional profiles of three cell lines derived from tumors from Osx-Cre p53fl/fl Rbfl/fl (fibroblastic OS) mouse model, and from pre-osteoblast cells (Kusa4b10 mouse bone marrow stromal cell line) and osteoblast cells (derived by in vitro differentiation of the Kusab410 mouse bone marrow stromal cell line) were generated by microarray analysis, each in triplicate, using Affymetrix mouse Gene1.0ST arrays. Transcriptional profiles were analyzed in cell lines derived from tumors from a genetically engineered mouse model of human osteosarcoma (Osx-Cre p53fl/fl Rbfl/fl) and osteoblast cells derived from the Kusa4b10 mouse bone marrow stromal cell line, in the undifferentiated state (pre-osteoblasts) and differentiated state (osteoblasts).

ORGANISM(S): Mus musculus

SUBMITTER: Alistair Chalk 

PROVIDER: E-GEOD-63939 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma.

Baker Emma K EK   Taylor Scott S   Gupte Ankita A   Chalk Alistair M AM   Bhattacharya Shreya S   Green Alanna C AC   Martin T John TJ   Strbenac Dario D   Robinson Mark D MD   Purton Louise E LE   Walkley Carl R CR  

Bone 20150105

Wnt pathway targeting is of high clinical interest for treating bone loss disorders such as osteoporosis. These therapies inhibit the action of negative regulators of osteoblastic Wnt signaling. The report that Wnt inhibitory factor 1 (WIF1) was epigenetically silenced via promoter DNA methylation in osteosarcoma (OS) raised potential concerns for such treatment approaches. Here we confirm that Wif1 expression is frequently reduced in OS. However, we demonstrate that silencing is not driven by D  ...[more]

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