Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx2.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
19 10 2021
19 10 2021
Historique:
received:
07
12
2019
accepted:
21
09
2021
entrez:
20
10
2021
pubmed:
21
10
2021
medline:
21
12
2021
Statut:
epublish
Résumé
Runx2 is an essential transcription factor for bone formation. Although osteocalcin, osteopontin, and bone sialoprotein are well-known Runx2-regulated bone-specific genes, the skeletal phenotypes of knockout (KO) mice for these genes are marginal compared with those of Runx2 KO mice. These inconsistencies suggest that unknown Runx2-regulated genes play important roles in bone formation. To address this, we attempted to identify the Runx2 targets by performing RNA-sequencing and found Smoc1 and Smoc2 upregulation by Runx2. Smoc1 or Smoc2 knockdown inhibited osteoblastogenesis. Smoc1 KO mice displayed no fibula formation, while Smoc2 KO mice had mild craniofacial phenotypes. Surprisingly, Smoc1 and Smoc2 double KO (DKO) mice manifested no skull, shortened tibiae, and no fibulae. Endochondral bone formation was also impaired at the late stage in the DKO mice. Collectively, these results suggest that Smoc1 and Smoc2 function as novel targets for Runx2, and play important roles in intramembranous and endochondral bone formation.
Identifiants
pubmed: 34667264
doi: 10.1038/s42003-021-02717-7
pii: 10.1038/s42003-021-02717-7
pmc: PMC8526618
doi:
Substances chimiques
Calcium-Binding Proteins
0
Core Binding Factor Alpha 1 Subunit
0
Osteonectin
0
Runx2 protein, mouse
0
SMOC-1 protein, mouse
0
Smoc2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1199Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : Grants-in-Aid for Scientific Research (C) 21K09827
Informations de copyright
© 2021. The Author(s).
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