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

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

First Page

123

Last Page

128

Download

Share

COinS