Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4-FOXO1/SMS1 axis in sphingomyelin biosynthesis.
FOXO1
ROR2
SMS1
dental pulp stem cells
senescence
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
09
05
2021
received:
30
12
2020
accepted:
30
05
2021
pubmed:
20
7
2021
medline:
1
2
2022
entrez:
19
7
2021
Statut:
ppublish
Résumé
Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well-recognized. ROR2 plays an important role in aging-related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self-renewal capacity, while its overexpression in aged DPSCs restores their self-renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4-FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging.
Identifiants
pubmed: 34278704
doi: 10.1111/acel.13430
pmc: PMC8373368
doi:
Substances chimiques
FOXO1 protein, human
0
Forkhead Box Protein O1
0
Sphingomyelins
0
ROR2 protein, human
EC 2.7.10.1
Receptor Tyrosine Kinase-like Orphan Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13430Informations de copyright
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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