State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Periodontology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Int J Oral Sci. 2021 Mar 9;13(1):7. doi: 10.1038/s41368-021-00114-8.
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.
牙齿根形态发生涉及两个生物学过程，即根伸长和牙本质生成，这两个过程由 Hertwig 上皮根鞘（HERS）的向下生长和正常成牙本质细胞分化来保证。已有报道表明，泛素依赖性蛋白降解能够精确调节各种生理过程，但其在牙齿发育中的作用仍不清楚。在这里，我们发现泛素特异性蛋白酶 34（USP34）在根形成中起着关键作用。在牙间质细胞中缺失 Usp34 会导致短根异常，其特征是根截断和根牙本质变薄。USP34 缺陷的牙髓细胞（DPC）表现出成牙本质分化减少，核因子 I/C（NFIC）下调。NFIC 的过表达部分恢复了 DPC 受损的成牙本质潜能。这些发现表明，USP34 依赖性去泛素化对于通过稳定 NFIC 来维持根形态发生至关重要。
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