Qin Qianyi, Yang Haoqing, Zhang Chen, Han Xiao, Guo Jing, Fan Zhipeng, Guo Jie
Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Oral Tissue Regeneration, and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, 250012, China.
Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, 100050, China.
Stem Cells Int. 2021 Apr 27;2021:5595580. doi: 10.1155/2021/5595580. eCollection 2021.
Alveolar bone remodeling under orthodontic force is achieved by periodontal ligament stem cells (PDLSCs), which are sensitive to mechanical loading. How to regulate functions of PDLSCs is a key issue in bone remodeling during orthodontic tooth movement. This study is aimed at investigating the roles of lncRNA Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) in the functional regulation of PDLSCs. First, HHIP-AS1 expression was downregulated in PDLSCs under continuous compressive pressure. Then, we found that the alkaline phosphatase activity, mineralization, and expression levels of bone sialoprotein, osteocalcin, and osterix were increased in PDLSCs by HHIP-AS1. The results of scratch migration and transwell chemotaxis assays revealed that HHIP-AS1 inhibited the migration and chemotaxis abilities of PDLSCs. In addition, the RNA sequencing data showed that 356 mRNAs and 14 lncRNAs were upregulated, including receptor tyrosine kinase-like orphan receptor 2 and nuclear-enriched abundant transcript 1, while 185 mRNAs and 6 lncRNAs were downregulated, including fibroblast growth factor 5 and LINC00973, in HHIP-AS1-depleted PDLSCs. Bioinformatic analysis revealed several biological processes and signaling pathways related to HHIP-AS1 functions, including the PI3K-Akt signaling pathway and JAK-STAT signaling pathway. In conclusion, our findings indicated that HHIP-AS1 was downregulated in PDLSCs under compressive pressure, and it promoted the osteogenic differentiation potential and inhibited the migration and chemotaxis abilities of PDLSCs. Thus, HHIP-AS1 may be a potential target for accelerating tooth movement during orthodontic treatment.
正畸力作用下的牙槽骨重塑是由对机械负荷敏感的牙周膜干细胞（PDLSCs）实现的。如何调节PDLSCs的功能是正畸牙移动过程中骨重塑的关键问题。本研究旨在探讨长链非编码RNA刺猬相互作用蛋白反义RNA 1（HHIP-AS1）在PDLSCs功能调节中的作用。首先，在持续压缩压力下，PDLSCs中HHIP-AS1的表达下调。然后，我们发现HHIP-AS1可使PDLSCs中的碱性磷酸酶活性、矿化以及骨唾液蛋白、骨钙素和osterix的表达水平增加。划痕迁移和transwell趋化试验结果显示，HHIP-AS1抑制了PDLSCs的迁移和趋化能力。此外，RNA测序数据表明，在HHIP-AS1缺失的PDLSCs中，有356个mRNA和14个lncRNA上调，包括受体酪氨酸激酶样孤儿受体2和核富集丰富转录本1，而185个mRNA和6个lncRNA下调，包括成纤维细胞生长因子5和LINC00973。生物信息学分析揭示了几个与HHIP-AS1功能相关的生物学过程和信号通路，包括PI3K-Akt信号通路和JAK-STAT信号通路。总之，我们的研究结果表明，在压缩压力下PDLSCs中HHIP-AS1表达下调，它促进了PDLSCs的成骨分化潜能，并抑制了其迁移和趋化能力。因此，HHIP-AS1可能是正畸治疗中加速牙齿移动的潜在靶点。
