Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts.
Animals
Animals, Newborn
Autocrine Communication
Base Sequence
Cell Differentiation
Feedback, Physiological
Gene Expression Regulation, Developmental
Growth Differentiation Factor 2
/ genetics
Humans
Mice
Mice, Inbred C57BL
Osteoblasts
/ cytology
Osteocalcin
/ genetics
Osteogenesis
/ genetics
Primary Cell Culture
Promoter Regions, Genetic
Ribosomal Proteins
/ genetics
Signal Transduction
/ genetics
Skull
/ cytology
Smad6 Protein
/ genetics
Smad7 Protein
/ genetics
Transcription Factor HES-1
/ genetics
Bone Morphogenetic Protein 9
Hes1
bone regeneration
notch
osteogenic differentiation
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
06
07
2020
revised:
01
11
2020
accepted:
18
11
2020
pubmed:
3
12
2020
medline:
28
7
2021
entrez:
2
12
2020
Statut:
ppublish
Résumé
Bone morphogenetic protein (BMP) 9 is one of the most osteogenic BMPs, but its mechanism of action has not been fully elucidated. Hes1, a transcriptional regulator with a basic helix-loop-helix domain, is a well-known effector of Notch signaling. Here, we find that BMP9 induces periodic increases of Hes1 mRNA and protein expression in osteoblasts, presumably through an autocrine negative feedback mechanism. BMP9-mediated Hes1 induction is significantly inhibited by an ALK inhibitor and overexpression of Smad7, an inhibitory Smad. Luciferase and ChIP assays revealed that two Smad-binding sites in the 5' upstream region of the mouse Hes1 gene are essential for transcriptional activation by BMP9. Thus, our data indicate that BMP9 induces Hes1 expression in osteoblasts via the Smad signaling pathway.
Identifiants
pubmed: 33264418
doi: 10.1002/1873-3468.14016
doi:
Substances chimiques
Gdf2 protein, mouse
0
Growth Differentiation Factor 2
0
Hes1 protein, mouse
0
Ribosomal Proteins
0
Rpl13a protein, mouse
0
Smad6 Protein
0
Smad6 protein, mouse
0
Smad7 Protein
0
Smad7 protein, mouse
0
Transcription Factor HES-1
0
Osteocalcin
104982-03-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
389-403Informations de copyright
© 2020 Federation of European Biochemical Societies.
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