Details

Autor(en) / Beteiligte

• Dong, Xing‐yue
• Huang, Yan‐xia
• Yang, Zhan
• Chu, Xiao‐yang
• Wu, Jue
• Wang, Shan
• He, Xin
• Gao, Chun‐Yan
• Chen, Xu
• Yang, Kai
• Zhang, Dong‐liang

Titel

Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4‐FOXO1/SMS1 axis in sphingomyelin biosynthesis

Ist Teil von

• Aging cell, 2021-08, Vol.20 (8), p.e13430-n/a

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. Proposed hypothesis for ROR2 suppressing ageing process by promoting sphingomyelin synthesis through inactivating STK4/FOXO1 signallingin in DPSCs. ROR2 decreases with age, and overexpression of ROR2 restores the differentiation and regeneration of senescent DPSC. ROR2 prevents the translocation of FOXO1 to the nucleus by inhibiting STK4 phosphorylation. FOXO1 binds to the promoter of SMS1, which catalyzes SM biogenesis, and represses its transcription. The ROR2/STK4‐FOXO1/SMS1 axis regulated SM biogenesis and DPSC senescence.