The molecular mechanisms underlying osteogenic differentiation of periodontal ligament stem cells (PDLSCs) under mechanical tension remain unclear. This study aimed to identify a potential long non-coding ribonucleic acids (lncRNAs)/circular RNAs (circRNAs)-microRNAs (miRNAs)-messenger RNAs (mRNAs) network in mechanical tension-induced osteogenic differentiation of PDLSCs. PDLSCs were isolated from the healthy human periodontal ligament, identified, cultured, and exposed to tensile force. The expression of osteogenic markers was examined, and whole transcriptome sequencing was performed to identify the expression patterns of lncRNA, circRNA, miRNAs, and mRNAs. Enrichment analyses were also performed. Candidate targets of differentially expressed non-coding RNAs (ncRNAs) were predicted, and potential competitive endogenous RNA (ceRNA) networks were constructed by Cytoscape. We found that the osteogenic differentiation of PDLSCs was significantly enhanced under dynamic tension (magnitude: 12%, frequency: 0.7 Hz). Overall, 344 lncRNAs, 57 miRNAs, 41 circRNAs, and 70 mRNAs were differentially expressed in the tension group and the control group. Functional enrichment analysis showed that differentially expressed mRNAs were mainly enriched in osteogenesis-related and mechanical stress-related biological processes and signal transduction pathways (e.g., tumor necrosis factor [TNF] and Hippo signaling pathways). The lncRNA/circRNA-miRNA-mRNA networks were depicted, and potential key ceRNA networks were identified. Our findings may help to further explore the underlying regulatory mechanism of osteogenic differentiation of PDLSCs under mechanical tensile stress.

Mechanical stress enhances bone metabolism and periodontal tissue remodelling. 1 The periodontal ligament (PDL) and alveolar bone sense loading stimuli and regulate bone reconstruction, which is the biological basis of orthodontic tooth movement (OTM). 2 These processes involve intricate mechanotransduction, and the turnover rate of the periodontium determines the quantity and quality of OTM. 3 Traditional orthodontic treatment often takes approximately 2 years, and the prolonged duration increases the risk of dental caries, periodontitis, and root resorption. 4 Therefore, researchers are constantly seeking ways to accelerate OTM.The origin of periodontal ligament distraction (PDLD) in accelerating OTM dates back to the end of the 20th century. 5 Studies have