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Issue 13, 2020
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Dicalcium silicate microparticles modulate the differential expression of circRNAs and mRNAs in BMSCs and promote osteogenesis via circ_1983–miR-6931–Gas7 interaction

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Abstract

Dicalcium silicate microparticle (C2S)-based biomaterials have a potential for bone and dental tissue regenerative applications. The C2S-mediated transcriptome level mechanism in mesenchymal stem cells (MSCs) during bone-defect healing has not been investigated yet. In this study, we elucidated the differential expression pattern of messenger RNAs (mRNAs) and circular RNAs (circRNAs) in C2S-treated MSCs and their involvement in the osteogenesis process. C2S robustly enhanced the osteogenic differentiation of MSCs and cranial bone defect healing. C2S-treatment modulated the differential expression of mRNAs and circRNAs in MSCs. Differentially expressed circRNAs and mRNAs were involved in competing endogenous RNA (ceRNA-interaction networks). These ceRNA-interaction networks regulated the signaling pathways associated with osteogenesis, e.g., Wnt, PI3K-Akt, MAPK, and JAK/STAT signaling. C2S-treatment upregulated the expression of circ_1983, Gas7, and Runx2 in BMSCs. RNase R and luciferase activity assay confirmed the stability and miR-6931 sponging property of circ_1983, respectively. Knockdown of circ_1983 enhanced miR-6931 expression but inhibited Gas7 and Runx2 expression and osteogenic differentiation in C2S-treated MSCs. In conclusion, for the first time, we report the role of cicr_1983–miR-6931–Gas7 ceRNA-interaction in C2S-induced osteogenic differentiation of MSCs and bone defect healing. This study opens a new research stream “the role of circRNAs-mediated ceRNA-interaction in biomaterials and stem cell-based bone tissue engineering”.

Graphical abstract: Dicalcium silicate microparticles modulate the differential expression of circRNAs and mRNAs in BMSCs and promote osteogenesis via circ_1983–miR-6931–Gas7 interaction

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Supplementary files

Article information


Submitted
21 Mar 2020
Accepted
19 May 2020
First published
20 May 2020

Biomater. Sci., 2020,8, 3664-3677
Article type
Paper

Dicalcium silicate microparticles modulate the differential expression of circRNAs and mRNAs in BMSCs and promote osteogenesis via circ_1983–miR-6931–Gas7 interaction

W. Zhong, X. Li, J. L. Pathak, L. Chen, W. Cao, M. Zhu, Q. Luo, A. Wu, Y. Chen, L. Yi, M. Ma and Q. Zhang, Biomater. Sci., 2020, 8, 3664
DOI: 10.1039/D0BM00459F

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