Abstract
Orthodontic tooth movement is achieved by periodontal tissue remodeling triggered by mechanical force. It is essential to investigate the reaction of periodontal ligament stem cells (PDLSCs) for improving orthodontic therapeutic approaches. Autophagy is an endogenous defense mechanism to prevent mechanical damage of environmental change. Long non-coding RNAs (lncRNAs) are key regulators in gene regulation, but their roles are still largely uncharacterized in the reaction of PDLSCs during orthodontic tooth movement. In this study, we showed that autophagy was significantly induced in PDLSCs under compressive force, as revealed by the markers of autophagy, microtubule-associated protein light chain 3 (LC3) II/I and Beclin1, and the formation of autophagosomes. After the application of compressive force, lncRNA FER1L4 was strongly upregulated. Overexpression of FER1L4 increased the formation of autophagosome and autolysosomes in PDLSCs, while knockdown of FER1L4 reversed the autophagic activity induced by mechanical force. In mechanism, FER1L4 inhibited the phosphorylation of protein kinase B (AKT) and subsequently increased the nuclear translocation of forkhead box O3 (FOXO3) and thus mediated autophagic cascades under compressive strain. In mouse model, the expression of Lc3 as well as Fer1l4 was increased in the pressure side of periodontal ligament during tooth movement. These findings suggest a novel mechanism of autophagy regulation by lncRNA during periodontal tissue remodeling of orthodontic treatment.
Highlights
Orthodontic tooth movement is achieved by the application of mechanical force, followed by periodontal tissue remodeling and regeneration (Krishnan and Davidovitch, 2006)
We have used RNA sequencing to detect the RNA landscape of Periodontal ligament stem cells (PDLSCs) exposed to static compressive force, and the results showed that 519 mRNAs and 90 Long non-coding RNAs (lncRNAs) were differentially expressed (Huang et al, 2019)
Autophagy Is Induced in PDLSCs Under Compressive Force
Summary
Orthodontic tooth movement is achieved by the application of mechanical force, followed by periodontal tissue remodeling and regeneration (Krishnan and Davidovitch, 2006). Orthodontic force transferred from the teeth to the surrounding bone is mediated by the periodontal ligament (Krishnan and Davidovitch, 2009), which is a flexible connective tissue that attaches the root. FER1L4 Regulates Autophagy of PDLSCs cementum to the alveolar bone (Beertsen et al, 1997). It induces bone deposition on the tension side and bone resorption on the compressive side when orthodontic force applied (Krishnan and Davidovitch, 2006, 2009). Further investigation of the response of PDLSCs to the orthodontic force and a better understanding of this mechanism are essential to improve orthodontic therapeutic approaches
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