circRNA422 enhanced osteogenic differentiation of bone marrow mesenchymal stem cells during early osseointegration through the SP7/LRP5 axis

Circular RNAs (circRNAs) play an important role in biological activities, especially in regulating osteogenic differentiation of stem cells. However, no studies have reported the role of circRNAs in early osseointegration. Here we identified a new circRNA, circRNA422, from rat bone marrow mesenchyma...

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Published in:Molecular therapy 2022-10, Vol.30 (10), p.3226-3240
Main Authors: Yu, Ke, Jiang, Zhiwei, Miao, Xiaoyan, Yu, Zhou, Du, Xue, Lai, Kaichen, Wang, Ying, Yang, Guoli
Format: Article
Language:English
Subjects:
Alkaline Phosphatase - metabolism
Alkaline Phosphatase - pharmacology
Animals
Bone Marrow Cells - metabolism
bone marrow mesenchymal stem cells
Cell Differentiation - genetics
Cells, Cultured
circular RNAs
Low Density Lipoprotein Receptor-Related Protein-5 - metabolism
Mesenchymal Stem Cells - metabolism
Original
osseointegration
Osseointegration - genetics
Osteogenesis - genetics
Rats
RNA, Circular - genetics
Sp7 Transcription Factor - metabolism
SP7/LRP5 axis
Titanium - chemistry
Titanium - metabolism
Titanium - pharmacology
titanium implant
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Summary:Circular RNAs (circRNAs) play an important role in biological activities, especially in regulating osteogenic differentiation of stem cells. However, no studies have reported the role of circRNAs in early osseointegration. Here we identified a new circRNA, circRNA422, from rat bone marrow mesenchymal stem cells (BMSCs) cultured on sandblasted, large-grit, acid-etched titanium surfaces. The results showed that circRNA422 significantly enhanced osteogenic differentiation of BMSCs with increased expression levels of alkaline phosphatase, the SP7 transcription factor (SP7/osterix), and lipoprotein receptor-related protein 5 (LRP5). Silencing of circRNA422 had opposite effects. There were two SP7 binding sites on the LRP5 promoter, indicating a direct regulatory relationship between SP7 and LRP5. circRNA422 could regulate early osseointegration in in vivo experiments. These findings revealed an important function of circRNA422 during early osseointegration. Therefore, circRNA422 may be a potential therapeutic target for enhancing implant osseointegration. [Display omitted] Yu et al. identified a new circRNA, circRNA422, from rat BMSCs cultured on SLA titanium surfaces. circRNA422 interfering inhibited osteogenic differentiation of BMSCs through the SP7/LRP5 axis. circRNA422 overexpression promoted early osseointegration in vivo, indicating its potential therapeutic application for enhancing implant osseointegration.
ISSN:1525-0016
1525-0024
1525-0024
DOI:10.1016/j.ymthe.2022.05.020