1. Academic Validation
  2. USP12 regulates ER stress-associated osteogenesis in human periodontal ligament cells under tension stress

USP12 regulates ER stress-associated osteogenesis in human periodontal ligament cells under tension stress

  • Cell Signal. 2023 Dec 17:114:111015. doi: 10.1016/j.cellsig.2023.111015.
Xiaoyu Liu 1 Beike Wang 2 Maolin Chang 2 Xiaocen Zhang 1 Hao Zou 1 Zhen Zhang 2 Guangli Han 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan, China; Orthodontic Department Division II, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan, China; Orthodontic Department Division II, School & Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: guanglihan@whu.edu.cn.
Abstract

The bone formation (osteogenesis) of human periodontal ligament cells (hPDLCs) under tension stress is essential for alveolar bone remodeling during orthodontic tooth movement (OTM). Deubiquitinating Enzymes (DUBs) remove ubiquitin from target proteins, affecting their function and mediating cell survival and differentiation. However, whether and how DUBs regulate hPDLC function under tension force is poorly understood. In this study, we first investigated the expression of DUBs in hPDLCs under cyclic tension stimulation (CTS). Up-regulation of USP12 was observed in hPDLCs and at the tension side of molar teeth in OTM C57BL6 mice models. Knockdown (KD) of USP12 led to enhanced osteogenesis of hPDLCs under CTS. RNA-seq analysis suggested that the unfolded protein response (UPR) was the prevailing biological process in hPDLCs with USP12 KD, indicating that USP12 depletion triggered endoplasmic reticulum (ER) stress. The three major UPR-related signaling branches, namely PERK/eIF2α/ATF4, IRE1α/XBP1s, and ATF6 axis, were activated in hPDLCs with USP12 KD. By utilizing specific inhibitors, we proved that the PERK/eIF2α/ATF4 axis predominantly mediated the enhanced osteogenesis in hPDLCs with USP12 KD under CTS. In summary, our study demonstrates that USP12 serves as a key regulator for CTS-induced osteogenesis in hPDLCs, suggesting that USP12 upregulation serves as an adaptive mechanism for hPDLCs to alleviate ER stress during OTM.

Keywords

Cyclic tension; Endoplasmic rediculum stress; Human periodontal ligament cells; Orthodontic tooth movement; Osteogenesis; Ubiquitin-specific peptidase12 (USP12).

Figures
Products
Inhibitors & Agonists
Other Products