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

Liangkun Xie,Zheng Guan,Nattawut Thuaksuban,Sha Lyu,Suttatip Kamolmattayakul,Thongchai Nuntanaranont,Takashi Yazawa,Mingzhu Zhang

doi:10.1155/2020/6319395

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.

Highlights

Dental pulp stem cells (DPSCs) can differentiate into odontoblasts, chondrocytes, adipocytes, and osteoblasts [1, 2]
We studied the altered expression of exosomal circular RNA (circRNA) derived from DPSCs under osteogenic induction, further demonstrated a circRNA affected osteogenic differentiation of DPSCs, trying to uncover the mechanism of osteogenic differentiation of DPSCs for future clinical treatment of bone regeneration
The detected particle distribution coefficient (PDI) was between 0.08 and 0.7, which proved the moderate dispersion of the system and high confidence of the results

Summary

Introduction

Dental pulp stem cells (DPSCs) can differentiate into odontoblasts, chondrocytes, adipocytes, and osteoblasts [1, 2]. Besides those properties, DPSCs have unique characters compared with other sources of mesenchymal stem cells (MSCs), being more accessible with minimal trauma and having shown great potentiality in regenerative medicine for the treatment of various human diseases such as bone deficiencies [3]. The primary goal to regenerate new bone is to activate osteogenic differentiation of certain somatic stem cells such as bone marrow mesenchymal stem cells (BMSCs) [4]. While DPSC as a highpotential candidate for bone regeneration, the mechanism for osteogenic differentiation of DPSC has to be further studied for better utilization of DPSC in bone regenerative medicine. Different types of RNAs in exosomes are key factors contributed to those functions

Methods

Results

Discussion

Conclusion