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Expression of DGCR8‐Dependent MicroRNAs Is Indispensable for Osteoclastic Development and Bone‐Resorbing Activity
Author(s) -
Sugatani Toshifumi,
Hildreth Blake E.,
Toribio Ramiro E.,
Malluche Hartmut H.,
Hruska Keith A.
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24759
Subject(s) - drosha , dicer , microrna , osteoclast , bone resorption , biology , microbiology and biotechnology , bone remodeling , gene expression , phenotype , gene silencing , regulation of gene expression , gene , small interfering rna , genetics , rna , rna interference , in vitro
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. J. Cell. Biochem. 115: 1043–1047, 2014. © 2013 Wiley Periodicals, Inc.