A microRNA regulatory mechanism of osteoblast differentiation.
Growing evidence shows that microRNAs (miRNAs) regulate various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; however, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast differentiation remains elusive. Here, through comprehensive analysis of miRNAs expression during osteoblast differentiation, we show that miR-206, previously viewed as a muscle-specific miRNA, is a key regulator of this process. miR-206 was expressed in osteoblasts, and its expression decreased over the course of osteoblast differentiation. Overexpression of miR-206 in osteoblasts inhibited their differentiation, and conversely, knockdown of miR-206 expression promoted osteoblast differentiation. In silico analysis and molecular experiments revealed connexin 43 (Cx43), a major gap junction protein in osteoblasts, as a target of miR-206, and restoration of Cx43 expression in miR-206-expressing osteoblasts rescued them from the inhibitory effect of miR-206 on osteoblast differentiation. Finally, transgenic mice expressing miR-206 in osteoblasts developed a low bone mass phenotype due to impaired osteoblast differentiation. Our data show that miRNA is a regulator of osteoblast differentiation.
Inose
Hiroyuki
H
Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Ochi
Hiroki
H
Kimura
Ayako
A
Fujita
Koji
K
Xu
Ren
R
Sato
Shingo
S
Iwasaki
Makiko
M
Sunamura
Satoko
S
Takeuchi
Yasuhiro
Y
Fukumoto
Seiji
S
Saito
Kuniaki
K
Nakamura
Takashi
T
Siomi
Haruhiko
H
Ito
Hiroshi
H
Arai
Yoshiyasu
Y
Shinomiya
Ken-ichi
K
Takeda
Shu
S
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics
D018031:Connexin 43; D035683:MicroRNAs; C540669:Mirn206 microRNA, mouse