OTUB1 Promotes Odontogenesis in Dental Pulp Stem Cells by Mediating TPM1 Deubiquitination and Activating Autophagy.

OBJECTIVES: DPSCs, known for their robust multipotent differentiation, are top candidates for engineering dental pulp tissues. OTUB1 is a critical deubiquitinating enzyme that regulates multiple biological processes and disease contexts. In our study, the function of OTUB1 in regulating the odontogenesis of DPSCs was investigated. MATERIALS AND METHODS: The verification of phenotypes involved experiments with gain and loss of function, along with a rat tooth pulp model. Proteomic analysis combined with LC-MS/MS analysis was conducted to identify the target in the process of OTUB1 mediated-deubiqutination in DPSCs. RESULTS: Odontogenic differentiation capacities were influenced by the increase or decrease of OTUB1. Increased levels of OTUB1 promote dentin formation in a rat tooth pulp model. Moreover, OTUB1 directly interacts with TPM1. By deubiquitinating TPM1, OTUB1 prevents its proteasomal degradation, thereby upregulating TPM1 protein levels and increasing autophagy in DPSCs. Consequently, the beneficial impact on odontogenic differentiation due to OTUB1 overexpression was nullified by the targeted removal of TPM1 or the inhibition of autophagy in DPSCs. CONCLUSIONS: The OTUB1-mediated deubiquitination/TPM1/autophagy pathway promotes odontogenic differentiation in DPSCs, thereby presenting novel strategies for enhancing dentin regeneration.