Early induction of Hes1 by bone morphogenetic protein 9 plays a regulatory role in osteoblastic differentiation of a mesenchymal stem cell line

Author:

Seong Chang‐Hwan12ORCID,Chiba Norika2,Fredy Mardiyantoro123,Kusuyama Joji24ORCID,Ishihata Kiyohide1,Kibe Toshiro1,Amir Muhammad Subhan125,Tada Ryohei12,Ohnishi Tomokazu2,Nakamura Norifumi1,Matsuguchi Tetsuya2

Affiliation:

1. Department of Oral and Maxillofacial Surgery Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan

2. Department of Oral Biochemistry Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan

3. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Airlangga University Surabaya Indonesia

4. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Brawijaya University Malang Indonesia

5. Department of Biosignals and Inheritance Tokyo Medical and Dental University (TMDU) Tokyo Japan

Abstract

AbstractBone morphogenic protein 9 (BMP9) is one of the most potent inducers of osteogenic differentiation among the 14 BMP members, but its mechanism of action has not been fully demonstrated. Hes1 is a transcriptional regulator with basic helix‐loop‐helix (bHLH) domain and is a well‐known Notch effector. In this study, we investigated the functional roles of early induction of Hes1 by BMP9 in a mouse mesenchymal stem cell line, ST2. Hes1 mRNA was transiently and periodically induced by BMP9 in ST2, which was inhibited by BMP signal inhibitors but not by Notch inhibitor. Interestingly, Hes1 knockdown in ST2 by siRNA increased the expression of osteogenic differentiation markers such as Sp7 and Ibsp and matrix mineralization in comparison with control siRNA transfected ST2. In contrast, forced expression of Hes1 by using the Tet‐On system suppressed the expression of osteogenic markers and matrix mineralization by BMP9. We also found that the early induction of Hes1 by BMP9 suppressed the expression of Alk1, an essential receptor for BMP9. In conclusion, BMP9 rapidly induces the expression of Hes1 via the SMAD pathway in ST2 cells, which plays a negative regulatory role in osteogenic differentiation of mesenchymal stem cells induced by BMP9.

Publisher

Wiley

Subject

Cell Biology,Molecular Biology,Biochemistry

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