Transforming growth factor-beta enables NFATc1 expression during osteoclastogenesis.

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.

authors

Fox SW,Evans KE,Lovibond AC

doi

10.1016/j.bbrc.2007.11.120

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

123-8

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)02521-1

journal_volume

366

pub_type

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