USP34 regulates tooth root morphogenesis by stabilizing NFIC

Shuang Jiang,Xingying Qi,Quan Yuan,Yuchen Guo,Jun Wang,Rui Sheng

doi:10.1038/s41368-021-00114-8

Abstract

Tooth root morphogenesis involves two biological processes, root elongation and dentinogenesis, which are guaranteed by downgrowth of Hertwig’s epithelial root sheath (HERS) and normal odontoblast differentiation. Ubiquitin-dependent protein degradation has been reported to precisely regulate various physiological processes, while its role in tooth development is still elusive. Here we show ubiquitin-specific protease 34 (USP34) plays a pivotal role in root formation. Deletion of Usp34 in dental mesenchymal cells leads to short root anomaly, characterized by truncated roots and thin root dentin. The USP34-deficient dental pulp cells (DPCs) exhibit decreased odontogenic differentiation with downregulation of nuclear factor I/C (NFIC). Overexpression of NFIC partially restores the impaired odontogenic potential of DPCs. These findings indicate that USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.

Highlights

Formation of the tooth root enables the tooth anchor to alveolar bones via periodontal ligament, making it an indispensable process in tooth eruption and development of the lower face
Expression of ubiquitinspecific protease 34 (USP34) in dental pulp To identify the potential role of USP34 in tooth root formation, we first performed immunohistochemistric staining of USP34 in the
USP34 regulates the protein level of nuclear factor I/C (NFIC) To unveil the molecular change of this phenotype, we examined several proteins which are involved in tooth development and regulated by ubiquitin

Summary

1234567890();,: INTRODUCTION

Formation of the tooth root enables the tooth anchor to alveolar bones via periodontal ligament, making it an indispensable process in tooth eruption and development of the lower face. Tooth tissue regeneration has been presented as a promising treatment.[1,2] It has been demonstrated that separated dental mesenchyme and epithelium can form teeth when recombined and cultured.[3,4] elucidating the process of root morphogenesis and the complicated mechanisms involved is a prerequisite for rapidly and efficiently evaluating and developing oral clinical therapies. Conditional knocking out Wnt10a, Wls or inhibiting Wnt/β-catenin signaling through DKK1 affected cell proliferation and differentiation, and disrupt dentin formation and root morphogenesis.[13,14,15,16] Deficiency of Smad[7], a general antagonist against TGF-β signaling, led to reduced tooth size and affected cell proliferation.[17] The question that remains to be answered is when and how these molecules achieve their specificity during tooth development. We demonstrated that USP34 deubiquitinates and stabilizes NFIC during odontoblast differentiation

RESULTS

DISCUSSION

CONCLUSION

MATERIALS AND METHODS