Induction of c-Fos and NFATc1 during RANKL-stimulated osteoclast differentiation is mediated by the p38 signaling pathway

Hao Huang, Eun-Ju Chang, Jiyoon Ryu, Zang Hee Lee, Youngkyun Lee, Hong-Hee Kim
Biochemical and Biophysical Research Communications 2006 December 8, 351 (1): 99-105
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 kappaB 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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"