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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.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-05-20 , DOI: 10.1039/d0bm00459f Wenchao Zhong 1 , Xingyang Li , Janak L Pathak , Liangjiao Chen , Wei Cao , Mingjing Zhu , Qianting Luo , Antong Wu , Yunxin Chen , Lingbo Yi , Manyuan Ma , Qingbin Zhang
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-05-20 , DOI: 10.1039/d0bm00459f Wenchao Zhong 1 , Xingyang Li , Janak L Pathak , Liangjiao Chen , Wei Cao , Mingjing Zhu , Qianting Luo , Antong Wu , Yunxin Chen , Lingbo Yi , Manyuan Ma , Qingbin Zhang
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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”.
中文翻译：
硅酸钙微颗粒通过circ_1983-miR-6931-Gas7相互作用调节BMSC中circRNA和mRNA的差异表达并促进成骨作用。
硅酸二钙微粒（C 2 S）基生物材料具有骨骼和牙齿组织再生应用的潜力。尚未研究骨缺损愈合过程中间充质干细胞（MSCs）中C 2 S介导的转录组水平机制。在这项研究中，我们阐明了经C 2 S处理的MSC中信使RNA（mRNA）和环状RNA（circRNA）的差异表达模式及其在成骨过程中的作用。C 2 S强有力地增强了MSC的成骨分化和颅骨缺损愈合。C 2S处理可调节MSC中mRNA和circRNA的差异表达。差异表达的circRNA和mRNA参与竞争性内源RNA（ceRNA相互作用网络）。这些ceRNA相互作用网络调节与成骨有关的信号传导途径，例如Wnt，PI3K-Akt，MAPK和JAK / STAT信号传导。C 2 S处理上调了BMSCs中circ_1983，Gas7和Runx2的表达。RNase R和荧光素酶活性测定分别证实了circ_1983的稳定性和miR-6931的海绵化特性。敲除circ_1983可增强miR-6931的表达，但可抑制Gas 7和Runx2的表达以及C 2中的成骨分化经S处理的MSC。总之，我们首次报道了cicr_1983–miR-6931–Gas7 ceRNA相互作用在C 2 S诱导的MSCs成骨分化和骨缺损愈合中的作用。这项研究开启了一个新的研究方向“ circRNAs介导的ceRNA相互作用在生物材料和基于干细胞的骨组织工程中的作用”。
更新日期：2020-06-30
中文翻译：
硅酸钙微颗粒通过circ_1983-miR-6931-Gas7相互作用调节BMSC中circRNA和mRNA的差异表达并促进成骨作用。
硅酸二钙微粒（C 2 S）基生物材料具有骨骼和牙齿组织再生应用的潜力。尚未研究骨缺损愈合过程中间充质干细胞（MSCs）中C 2 S介导的转录组水平机制。在这项研究中，我们阐明了经C 2 S处理的MSC中信使RNA（mRNA）和环状RNA（circRNA）的差异表达模式及其在成骨过程中的作用。C 2 S强有力地增强了MSC的成骨分化和颅骨缺损愈合。C 2S处理可调节MSC中mRNA和circRNA的差异表达。差异表达的circRNA和mRNA参与竞争性内源RNA（ceRNA相互作用网络）。这些ceRNA相互作用网络调节与成骨有关的信号传导途径，例如Wnt，PI3K-Akt，MAPK和JAK / STAT信号传导。C 2 S处理上调了BMSCs中circ_1983，Gas7和Runx2的表达。RNase R和荧光素酶活性测定分别证实了circ_1983的稳定性和miR-6931的海绵化特性。敲除circ_1983可增强miR-6931的表达，但可抑制Gas 7和Runx2的表达以及C 2中的成骨分化经S处理的MSC。总之，我们首次报道了cicr_1983–miR-6931–Gas7 ceRNA相互作用在C 2 S诱导的MSCs成骨分化和骨缺损愈合中的作用。这项研究开启了一个新的研究方向“ circRNAs介导的ceRNA相互作用在生物材料和基于干细胞的骨组织工程中的作用”。
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