MicroRNA-124 regulates osteoclast differentiation

• The expression of miR-124 dramatically decreased during RANKL-dependent osteoclast differentiation of mouse bone marrow macrophages.
• Exogenous miR-124 attenuated, while miR-124 inhibitors accelerated, osteoclastogenesis.
• miR-124-mediated inhibition of osteoclastogenesis was NFATc1-dependent.
• miR-124 also affected the proliferation and motility of osteoclast precursors, the latter being accompanied by reduced expression of RhoA and Rac1.

Osteoclasts are specialized cells for bone-resorption originated from precursors of macrophage/monocyte lineage. The receptor activator of NFκB ligand (RANKL) initiates osteoclast differentiation, in which nuclear factor of activated T cell cytoplasmic 1 (NFATc1) plays a key role as a master transcription factor. In the present report, we show that microRNA-124 (miR-124) regulates osteoclastogenesis of mouse bone marrow macrophages (BMMs) by suppressing NFATc1 expression. On the other hand, synthetic inhibitor that binds specifically to miR-124 enhanced osteoclast differentiation and NFATc1 expression. The overexpression of a constitutively active form of NFATc1 prevented the inhibitory effect of miR-124 on osteoclastogenesis. Finally, miR-124 also affected the proliferation and motility of osteoclast precursors, the latter coinciding with the reduced expression of RhoA and Rac1. These findings not only reveal unprecedented role of miR-124 in osteoclastogenesis but also suggest a novel mode of regulation of NFATc1 in osteoclasts.