Cyclic stretch-induced exosomes from periodontal ligament cells promote osteoblasts osteogenic differentiation via the miR-181d-5p/TNF signaling pathway

Objective: To investigate the effects of cyclic stretch-induced periodontal ligament cell (PDLC) exosomes on osteoblast differentiation, and to explore their regulatory role in mechanical force-related periodontal tissue remodeling.Design: After applying 20 % cyclic stretch loading to PDLCs, exosomes were extracted from the supernatant and co-cultured with osteoblasts to detect their effects on osteogenic differentiation. Meanwhile, the exosomes were sequenced by high-throughput microRNA sequencing for bioinformatic analysis and validation to explore exosome signaling pathways through miRNAs. Results: Cyclic stretch-induced PDLC exosomes could be taken up by osteoblasts and promoted osteogenic differentiation of osteoblasts, as demonstrated by the increased expression levels of osteogenesis-related factors and enhanced alkaline phosphatase (Alp) staining. Among the differentially expressed miRNAs between exosomes from cyclic stretch group and control group, miRNA-181d-5p was up-regulated significantly. The expression levels of osteogenesis-related factors and Alp staining were also increased in osteoblasts transfected with miR181d-5p, and this effect might be related to the inhibitory role of exosomal miR-181d-5p on tumor necrosis factor (TNF).Conclusions: Cyclic stretch-induced PDLC exosomes exhibited a promoting effect on osteogenic differentiation, which might result from the inhibition of TNF via exosomal miR-181d-5p.