Transforming growth factor-{beta} enables NFATc1 expression during osteoclastogenesis
- School of Biological Science, Ecotoxicology and Stress Biology Group, Room 404 Davy, University of Plymouth, PL4 8AA (United Kingdom)
- Department of Cellular Pathology, St. George's Hospital, SW17 0RE (United Kingdom)
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 24 h by regulating expression of NFATc1, a key osteoclastic transcription factor. TGF-{beta} directly induces cytoplasmic NFATc1 expression within 24 h, 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.
- OSTI ID:
- 21043601
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 366, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.11.120; PII: S0006-291X(07)02521-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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