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MicroRNA-145 regulates osteoblastic differentiation by targeting the transcription factor Cbfb
Toru Fukuda1, Hiroki Ochi1, Satoko Sunamura1
1Department 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.
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.
Insights
MicroRNA-145 (miR-145) inhibits osteoblast differentiation and bone formation by decreasing core binding factor beta (Cbfb) expression. This study reveals miR-145 as a key regulator in bone regeneration.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Osteoblast differentiation is crucial for bone formation and is regulated by hormones and transcription factors.
- Runt-related transcription factor 2 (Runx2) is essential for osteoblastogenesis, forming complexes with core binding factor beta (Cbfb).
- The molecular mechanisms regulating Cbfb expression remain largely unknown.
Purpose of the Study:
- To identify novel regulators of core binding factor beta (Cbfb) expression.
- To investigate the role of microRNAs in osteoblastogenesis and bone formation.
- To elucidate the regulatory network involving microRNAs and Cbfb in osteoblastic differentiation.
Main Methods:
- Quantitative real-time PCR to measure microRNA and gene expression.
- In vitro studies using osteoblast cell cultures.
- In vivo bone regeneration assays.
- Western blotting to assess protein levels.
Main Results:
- MicroRNA-145 (miR-145) expression significantly increased during osteoblastogenesis.
- Stable expression of miR-145 led to decreased Cbfb expression and inhibited osteoblast differentiation.
- miR-145, in conjunction with miR-34c, suppressed osteoblastogenesis.
- In vivo experiments demonstrated that miR-145 impaired bone regeneration.
Conclusions:
- miR-145 is identified as a critical regulator of Cbfb expression.
- miR-145 acts as an inhibitor of osteoblast differentiation and bone formation.
- A regulatory microRNA network involving miR-145 and Cbfb plays a physiological role in bone metabolism.
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