title: MicroRNA-124 regulates osteoclast differentiation.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea. ylee@knu.ac.kr
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Cheol Kyu
authors.initials: CK
authors.lastname: Park
authors.forename: Yong-Gun
authors.initials: YG
authors.lastname: Kim
authors.forename: Heon-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053245:RANK Ligand / Q000494:pharmacology*
chemical_list: D035683:MicroRNAs; D050778:NFATC Transcription Factors; D053245:RANK Ligand
keywords: Differentiation; NFATc1; Osteoclast; miR-124