lncRNA HHIP-AS1 Promotes the Osteogenic Differentiation Potential and Inhibits the Migration Ability of Periodontal Ligament Stem Cells

Abstract

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, in vitro 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.

Residual periodontal ligament in the extraction socket promotes the dentin regeneration potential of DPSCs in the rabbit jaw

“…The care and use of animals were performed strictly following the regulations on the management of experimental animals. Rabbit DPSCs and PDLSCs were obtained as previously described [ 26 , 27 ]. Incisors were extracted from 3-month-old New Zealand white rabbits after oral disinfection.…”

Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis

“…Recent studies have revealed that cells exhibit various biological reactions when exposed to different forces ( Huang et al, 2018 ), including mechanical forces such as continuous or intermittent compression forces, fluid shear force, mechanical vibration, cyclic tension stress, and static tensile strain ( Chen et al, 2021 ; Qin et al, 2021 ; Wu et al, 2021 ; Shi et al, 2022 ; Sun et al, 2022 ; Manokawinchoke et al, 2023 ). Mechanical force–induced OTM leads to a series of cell proliferation, differentiation, and apoptosis in periodontal tissues ( Deng et al, 2021 ).…”

JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens

“…He et al found that mechanical stress in chondrocytes combined with IL-4 to induce CITED2 gene expression in human chondrocytes via JAK/STAT pathway, thereby inhibiting matrix metalloproteinase (MMP13) production and providing chondroprotection against osteoarthritis (OA) (He et al, 2019). In addition, Qin et al also found that periodontal ligament stem cells (PDLSC) sensitive to Frontiers in Bioengineering and Biotechnology frontiersin.org mechanical loading may downregulate HHIP-AS1 and promote the osteogenic differentiation potential of PDLSCs under continuous compressive stress, possibly via the JAK/STAT pathway (Qin et al, 2021). The Zyxin/Ajuba family of LIM proteins is a class of proteins that responds to biophysical forces (Jia et al, 2020), and Ajuba can play an important role in cell migration and epithelial morphogenesis by separating JAK1 from the interferon receptor and acting as a bona fide inhibitor of IFN/JAK1/STAT1 function (Sahai and Marshall, 2002;Jia et al, 2020).…”