Periodontal Ligament Stem Cell-Derived Extracellular Vesicles Enhance Tension-Induced Osteogenesis

Tension-induced osteogenesis has great significance in maintaining bone homeostasis and ensuring the efficiency and stability of orthodontic treatment. Recently, extracellular vesicles (EVs) have shown great potential in regulating bone remodeling. Here, we aimed to explore the effects of periodontal ligament stem cell (PDLSC)-derived EVs on tension-induced osteogenesis and the potential mechanism. PDLSC-derived EVs were extracted by ultracentrifugation. In vitro, PDLSC-derived EVs of 10 μg/mL significantly improved the proliferation of MC3T3-E1 cells and enhanced the osteogenic differentiation of osteoblasts under a tensile strain of 2000 uε. Next, a mouse model of orthodontic tooth movement (OTM) was established and treated with subperiosteal injection of PDLSC-derived EVs (1 mg/kg) on the tension side. The results showed that treatment with PDLSC-derived EVs effectively enhanced OTM and promoted osteogenesis on the tension side, including increasing trabecular bone parameters and promoting the expression of osteogenic-related biomarkers (OCN and OPN). More interestingly, we identified several mechano-sensitive miRNAs enriched in PDLSC-derived EVs by high-throughput miRNA sequencing. Bioinformatics analysis indicated that they were related to various osteogenesis-related signaling pathways. Therefore, PDLSC-derived EVs could improve the efficiency of OTM by enhancing tension-induced osteogenesis of osteoblasts. Our study may provide potential evidence for the promoting effects of PDLSC-derived EVs on osteogenesis and offer new insights into the development of treatment strategies for enhancing osteogenesis in orthodontic treatment and other metabolic bone diseases.