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

Toru Fukuda; Hiroki Ochi; Satoko Sunamura; Akina Haiden; Waka Bando; Hiroyuki Inose; Atsushi Okawa; Yoshinori Asou; Shu Takeda

doi:10.1016/j.febslet.2015.09.024

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

FEBS Lett. 2015 Oct 24;589(21):3302-8. doi: 10.1016/j.febslet.2015.09.024. Epub 2015 Oct 9.

Authors

Toru Fukuda¹, Hiroki Ochi¹, Satoko Sunamura¹, Akina Haiden², Waka Bando³, Hiroyuki Inose⁴, Atsushi Okawa⁵, Yoshinori Asou⁵, Shu Takeda⁶

Affiliations

¹ Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan.
² Department of Emergency & Critical Care Medicine, School of Medicine, Keio University, Shinanomachi 35, Shinjyuku-ku, Tokyo 160-8582, Japan.
³ Section of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Keio University, Shinanomachi 35, Shinjyuku-ku, Tokyo 160-8582, Japan.
⁴ Department of Orthopedic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
⁵ Department of Orthopedic Surgery and Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
⁶ Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan. Electronic address: [email protected].

PMID: 26450370
DOI: 10.1016/j.febslet.2015.09.024

Abstract

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.

Keywords: Core binding factor beta; MicroRNA; Osteoblast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Bone Regeneration
Cell Differentiation
Cell Line
Core Binding Factor beta Subunit / genetics*
Core Binding Factor beta Subunit / metabolism
Gene Expression Regulation
HEK293 Cells
Humans
Mice
MicroRNAs / metabolism*
Osteoblasts / physiology*
Promoter Regions, Genetic

Substances

CBFB protein, human
Cbfb protein, mouse
Core Binding Factor beta Subunit
MIRN145 microRNA, human
MIRN145a microRNA, mouse
MicroRNAs