Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: PU.1 and NFATc1 mediate osteoclastic induction of the mouse β₃ integrin promoter
Other Titles: PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta(3) integrin promoter
Author: Crotti, T.
Sharma, S.
Fleming, J.
Flannery, M.
Ostrowski, M.
Goldring, S.
McHugh, K.
Citation: Journal of Cellular Physiology, 2008; 215(3):636-644
Publisher: Wiley-Liss
Issue Date: 2008
ISSN: 0021-9541
Statement of
Tania N. Crotti, Sudarshana M. Sharma, Joseph D. Fleming, Merrilee R. Flannery, Michael C. Ostrowski, Steven R. Goldring and Kevin P. McHugh
Abstract: Expression of the alpha(v)beta(3) integrin is required for normal osteoclast function. We previously showed that an evolutionary conserved NFATc1 binding site is required for RANKL induction and NFATc1 transactivation of the human beta(3) promoter. The mechanism conferring specificity for RANKL induction and NFATc1 transduction of the beta(3) gene in osteoclast differentiation is unclear since NFATc1 is expressed and activated in numerous cell types that do not express the beta(3) gene. PU.1 is an ETS family transcription factor in myeloid cells associated with expression of various osteoclast genes. The present study investigates the role of NFATc1 in concert with PU.1 in osteoclast-specific transcription of the mouse beta(3) integrin gene. The mouse beta(3) promoter was transactivated by NFATc1 in RAW264.7 cells and deletion or mutation of either of the conserved NFAT and PU.1 binding sites abrogated transactivation. NFATc1 transactivation of the mouse beta(3) promoter was specifically dependent on co-transfected PU.1 in HEK293 cells, to the exclusion of other ETS family members. Direct binding of NFATc1 and PU.1 to their cognate sequences was demonstrated by EMSA and NFATc1 and PU.1 occupy their cognate sites in RANKL-treated mouse marrow precursors in chromatin immuno-precipitation (ChIP) assays. TAT-mediated transduction with dominant-negative NFATc1 dose-dependently blocked endogenous expression of the mouse beta(3) integrin and the formation of TRAP positive multinucleated cells in RANKL-treated mouse macrophages. These data provide evidence that NFATc1, in concert with PU.1, are involved in regulation of beta(3) integrin expression during osteoclast differentiation and suggest that PU.1 confers specificity to the NFATc1 response to macrophage lineage cells.
Keywords: Cell Line
Mice, Inbred C57BL
Integrin beta3
Proto-Oncogene Proteins
Cell Differentiation
Gene Expression Regulation
Sequence Deletion
Binding Sites
Base Sequence
Base Pairing
Protein Binding
Sequence Homology, Nucleic Acid
Genes, Dominant
Molecular Sequence Data
NFATC Transcription Factors
Promoter Regions, Genetic
Transcriptional Activation
Description: The definitive version may be found at
DOI: 10.1002/jcp.21344
Appears in Collections:Aurora harvest
Pathology publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.