Exosomal circLPAR1 Promoted Osteogenic Differentiation of Homotypic Dental Pulp Stem Cells by Competitively Binding to hsa-miR-31

Abstract

Human dental pulp stem cells (DPSCs) hold great promise in bone regeneration. However, the exact mechanism of osteogenic differentiation of DPSCs remains unknown, especially the role of exosomes played in. The DPSCs were cultured and received osteogenic induction; then, exosomes from osteogenic-induced DPSCs (OI-DPSC-Ex) at different time intervals were isolated and sequenced for circular RNA (circRNA) expression profiles. Gradually, increased circular lysophosphatidic acid receptor 1 (circLPAR1) expression was found in the OI-DPSC-Ex coincidentally with the degree of osteogenic differentiation. Meanwhile, results from osteogenic differentiation examinations showed that the OI-DPSC-Ex had osteogenic effect on the recipient homotypic DPSCs. To investigate the mechanism of exosomal circLPAR1 on osteogenic differentiation, we verified that circLPAR1 could competently bind to hsa-miR-31, by eliminating the inhibitory effect of hsa-miR-31 on osteogenesis, therefore promoting osteogenic differentiation of the recipient homotypic DPSCs. Our study showed that exosomal circRNA played an important role in osteogenic differentiation of DPSCs and provided a novel way of utilization of exosomes for the treatment of bone deficiencies.

The Emerging Regulatory Role of Circular RNAs in Periodontal Tissues and Cells

“…These studies have focussed on the role of circRNA in controlling cell differentiation, which is important in the context of periodontal regeneration and tissue engineering. Herein, we undertook a scoping review of recent research into the role of circRNA in cell differentiation in vitro and periodontal tissue healing and regeneration in vivo, drawing information from 23 studies [ 37 , 38 , 39 , 40 , 41 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Much of the existing research has focused on osteogenic differentiation of periodontal stem cells, and how circRNAs might function as a sponge for miRNAs.…”

“…There is increasing evidence that circRNAs can be detected in human dental pulp stem cells (hDPSCs) during their osteo/odontogenic differentiation [ 59 , 60 , 61 , 62 , 63 , 64 , 65 ] ( Table 3 ). In these studies, hDPSCS were mostly isolated from dental pulp tissue removed from healthy or inflamed third molar teeth [ 64 , 65 ].…”

“…Xie et al [ 62 ] showed that exosomal hsa_circ_0003611 (also named circular lysophosphatidic acid receptor 1-circLPAR1) was increased during osteogenesis of hDPSCs after 14 days. Luciferase reporter assays demonstrated that circLPAR1 was the target of hsa-miR-31.…”

“…In summary, seven studies showed that circRNAs could be detected in hDPSCs isolated from healthy dental pulp tissues. One study detected exosomal circRNA [ 62 ]. There are a total of eight circRNAs that are known to be involved in the osteogenesis of hDPSCs, which function as sponges for miRNA.…”

Circular RNAs in stem cell differentiation: a sponge-like role for miRNAs

“…In yet another study, circRNA SIPA1L1 was found to regulate miR-617/Smad3 axis to potentiate osteogenic differentiation of DPSCs 20 . Furthermore, role of exosomes in osteogenic differentiation of DPSCs has been investigated and it was found that circLPAR1 adsorbs to hsa-miR-31 to avoid its inhibitory effects on osteogenesis of DPSCs 36 . A microarray analysis revealed 43 upregulated circRNAs and 144 downregulated circRNAs to be differentially expressed in human DPSCs during odontogenic differentiation process.…”