Abstract

Osteoclastogenesis is dependent on distinct stimuli that prime and activate osteoclast differentiation. One cytokine needed to prime monocytes for osteoclastogenesis is TGF-beta, which enables and augments RANKL and TNF-alpha-induced osteoclast differentiation. However, the precise time-period during which this occurs and the molecular mechanism mediating this action are unknown. We report here TGF-beta prime monocytes for osteoclast formation within 24h by regulating expression of NFATc1, a key osteoclastic transcription factor. TGF-beta directly induces cytoplasmic NFATc1 expression within 24h, but is unable to stimulate NFATc1 nuclear translocation. Furthermore, RANKL-induced NFATc1 expression is dependent on the presence of TGF-beta during the early stages of osteoclastogenesis. Similarly, TNF-alpha activates osteoclastogenesis by stimulating translocation of TGF-beta-induced NFATc1. In light of these findings, it is apparent that osteoclast formation is dependent on coordinated interactions between TGF-beta and RANKL/TNF-alpha that regulate the expression and intracellular distribution of NFATc1 during early stages of osteoclast differentiation.

DOI

10.1016/j.bbrc.2007.11.120

Publication Date

2008-02-01

Publication Title

Biochem Biophys Res Commun

Volume

366

Issue

1

First Page

123

Last Page

128

Organisational Unit

School of Biomedical Sciences

Keywords

Animals, Cell Differentiation, Cell Line, Cell Proliferation, Gene Expression Regulation, Developmental, Mice, Monocytes, NFATC Transcription Factors, Osteoclasts, Proto-Oncogene Proteins c-fos, Transforming Growth Factor beta

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