MicroRNA-145 regulates osteoblastic differentiation by targeting the transcription factor Cbfb

被引:67
作者
Fukuda, Toru [1 ,7 ]
Ochi, Hiroki [1 ,7 ]
Sunamura, Satoko [1 ,7 ]
Haiden, Akina [2 ]
Bando, Waka [3 ]
Inose, Hiroyuki [4 ]
Okawa, Atsushi [5 ,6 ]
Asou, Yoshinori [5 ,6 ]
Takeda, Shu [1 ,7 ]
机构
[1] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Bunkyo Ku, Tokyo 1138519, Japan
[2] Keio Univ, Sch Med, Dept Emergency & Crit Care Med, Shinjyuku Ku, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Dept Internal Med, Sect Nephrol Endocrinol & Metab,Shinjyuku Ku, Tokyo 1608582, Japan
[4] Tokyo Med & Dent Univ, Dept Orthoped Surg, Bunkyo Ku, Tokyo 1138519, Japan
[5] Tokyo Med & Dent Univ, Int Res Ctr Mol Sci Tooth & Bone Dis, Dept Orthoped Surg, Bunkyo Ku, Tokyo 1138519, Japan
[6] Tokyo Med & Dent Univ, Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence GCOE Program, Bunkyo Ku, Tokyo 1138519, Japan
[7] Japan Agcy Med Res & Dev, CREST, Chiyoda Ku, Tokyo 1000004, Japan
关键词
MicroRNA; Osteoblast; Core binding factor beta; MESENCHYMAL STEM-CELLS; BINDING-FACTOR-BETA; BONE-FORMATION; OSTEOGENIC DIFFERENTIATION; SKELETAL DEVELOPMENT; LINEAGE PROGRESSION; ANIMAL DEVELOPMENT; RUNX2; MICE; MASS;
D O I
10.1016/j.febslet.2015.09.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Osteoblastic differentiation is regulated by various factors, including hormones and transcription factors. Runt-related transcription factor 2 (Runx2) is an essential player in osteoblastogenesis and transactivates its molecular target by creating a protein complex with its hetero-dimeric partner core binding factor beta (Cbfb). However, the molecular regulation of Cbfb expression remains unknown. Here, we identified miR-145 as a crucial regulator of Cbfb expression. The expression of miR-145 increased during osteoblastogenesis, indicating that miR-145 works as an inhibitor of osteoblastogenesis. Stable expression of miR-145 decreased endogenous Cbfb expression and inhibited osteoblastogenesis, in cooperation with miR-34c. Furthermore, miR-145 decreased bone regeneration in vivo. Our results indicate that miR-145 physiologically regulates osteoblast differentiation and bone formation via Cbfb expression by forming a regulatory microRNA network. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3302 / 3308
页数:7
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