RRC ID 78201
Author Seong CH, Chiba N, Fredy M, Kusuyama J, Ishihata K, Kibe T, Amir MS, Tada R, Ohnishi T, Nakamura N, Matsuguchi T.
Title Early induction of Hes1 by bone morphogenetic protein 9 plays a regulatory role in osteoblastic differentiation of a mesenchymal stem cell line.
Journal J Cell Biochem
Abstract Bone 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.
Volume 124(9)
Pages 1366-1378
Published 2023-9-1
DOI 10.1002/jcb.30452
PMID 37565579
MeSH Animals Cell Differentiation / genetics Growth Differentiation Factor 2* / genetics Growth Differentiation Factor 2* / metabolism Interleukin-1 Receptor-Like 1 Protein / metabolism Mesenchymal Stem Cells* / metabolism Mice Osteogenesis / genetics RNA, Small Interfering / metabolism Transcription Factor HES-1 / genetics Transcription Factor HES-1 / metabolism
Resource
Human and Animal Cells ST2(RCB0224)