Induction of c-Fos and NFATc1 during RANKL-stimulated osteoclast differentiation is mediated by the p38 signaling pathway
- BK21 Program, Seoul National University, Seoul 110-749 (Korea, Republic of)
- Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of)
- BK21 Program, Seoul National University, Seoul 110-749 (Korea, Republic of) and Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749 (Korea, Republic of) and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of)
The crucial role of p38 mitogen-activated protein kinase for osteoclast differentiation has been suggested from studies with specific pharmacological inhibitors and dominant-negative forms of p38. However, the targets through which p38 regulates osteoclast differentiation have not been clearly revealed. Here, we show that inhibition of p38 activity with SB203580 reduced osteoclastogenesis from primary precursor cells, with concomitant suppression in the induction of both c-Fos and nuclear factor of activated T cells (NFAT) c1 by receptor activator of nuclear factor {kappa}B ligand (RANKL), the key osteoclast differentiation factor. Overexpression of dominant-negative forms of p38 upstream kinases MKK3 and MKK6 elicited similar reduction in RANKL-stimulated elevation of c-Fos and NFATc1. Interestingly, overexpression of c-Fos restored RANKL-induced osteoclast differentiation from and NFATc1 expression in SB203580-treated precursor cells. Our results demonstrate a previously unknown function of the p38 pathway in up-regulating c-Fos and NFATc1 expression during RANKL-induced osteoclastogenesis.
- OSTI ID:
- 20857900
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 351, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.10.011; PII: S0006-291X(06)02225-X; Copyright (c) 2006 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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