TY - JOUR
T1 - Expression of DGCR8-dependent microRNAs is indispensable for osteoclastic development and bone-resorbing activity
AU - Sugatani, Toshifumi
AU - Hildreth, Blake E.
AU - Toribio, Ramiro E.
AU - Malluche, Hartmut H.
AU - Hruska, Keith A.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - DGCR8
KW - Dicer
KW - microRNA
KW - osteoclast
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U2 - 10.1002/jcb.24759
DO - 10.1002/jcb.24759
M3 - Article
C2 - 24420069
AN - SCOPUS:84907422952
SN - 0730-2312
VL - 115
SP - 1043
EP - 1047
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 6
ER -