Mitf regulates osteoclastogenesis by modulating NFATc1 activity.

ABSTRACT: Transcription factors Mitf and NFATc1 share many downstream targets that are critical for osteoclastogenesis. Since RANKL signals induce/activate both NFATc1 and Mitf isoform-E (Mitf-E), a tissue-restricted Mitf isoform in osteoclasts, it is plausible that the two factors work together to promote osteoclastogenesis. Although Mitf was shown to function upstream of NFATc1 previously, this study showed that expression of Mitf had little effects on NFATc1 and NFATc1 was critical for the induction of Mitf-E. In Mitf(mi/mi) mice, the semi-dominant mutation in Mitf gene leads to arrest of osteoclastogenesis in the early stages. However, when stimulated by RANKL, the Mitf(mi/mi) preosteoclasts responded with a significant induction of NFATc1, despite that the cells cannot differentiate into functi

SUBMITTER: Lu SY 

PROVIDER: S-EPMC4177974 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature