title: Expression of DGCR8-dependent microRNAs is indispensable for osteoclastic development and bone-resorbing activity.
abstract: Recently, microRNAs (miRs) have been implicated in bone formation and homeostasis. We previously reported that Dicer generated miRs have pivotal roles in differentiation and activity of osteoclasts. However, recent studies have demonstrated that Dicer is implicated in production of endogenous small interfering RNAs, non-canonical miRs, and other small RNAs in mammals. Hence, a challenging question is the extent to which expression of canonical miRs is obligatory for osteoclastic control of bone metabolism. DiGeorge syndrome critical region gene 8 (DGCR8) is exclusively related to expression of miRs by a canonical processing pathway together with the nuclear RNase III enzyme Drosha. Osteoclast-specific deletion of DGCR8 led to impaired osteoclastic development and bone resorption so that bone development was significantly retarded. In culture, the expression levels of osteoclastic phenotype-related genes and proteins were remarkably inhibited during osteoclastogenesis in DGCR8-deficiency. Thus, we have identified that DGCR8-dependent miRs are indispensable for osteoclastic control of bone metabolism.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sugatani
authors.forename: Blake E
authors.initials: BE
authors.lastname: Hildreth
authors.forename: Ramiro E
authors.initials: RE
authors.lastname: Toribio
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D015151:Immunoblotting; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; D016601:RNA-Binding Proteins; D016173:Macrophage Colony-Stimulating Factor
keywords: DGCR8; Dicer; microRNA; osteoclast