Overexpression of prohibitin-1 inhibits RANKL-induced activation of p38-Elk-1-SRE signaling axis blocking MKK6 activity

Prohibitin-1 (PHB) regulates diverse cellular processes by controlling several signaling pathways. In this study, we investigated the functional involvement of PHB in osteoclast differentiation. PHB expression was time-dependently increased by RANKL in BMMs. However, the retroviral over-expression of PHB strongly inhibited the expression of c-Fos and NFATc1, and activation of p38-Elk-1-SRE signaling pathway. Anti-osteoclastogenic action of PHB was significantly inhibited by constitutively active forms of MKK6, but not Elk-1. Collectively, PHB negatively regulates the formation of mature osteoclasts via inhibition of MKK6 activity that affects the activation of the p38-Elk-1 signaling axis required for the expression of c-Fos and NFATc1. [Display omitted] •We first investigated the functional involvement of prohibitin-1 in osteoclast differentiation.•Our data demonstrate for the first time that prohibitin-1 inhibits osteoclastogenesis.•Prohibitin-1 acts as an inhibitor of c-Fos and NFATc1 activation.•Prohibitin-1 inhibits activation of the MKK6-p38-Elk-1-c-Fos SRE signaling axis.•Prohibitin-1 deserves new evaluation as a potential treatment target in various bone diseases.