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MiRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1? pathway and enhances bone regeneration in critical size defects.


ABSTRACT: BACKGROUND:Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge. Many studies have emphasized the osteogenic and angiopoietic abilities of stem cells for tissue regeneration. We previously showed that microRNA-21 (miRNA-21) can promote angiogenesis in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). In the present study, the role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated. METHODS:Western blotting and qPCR were performed to investigate the influences of miRNA-21 on osteogenic differentiation of BMSCs. The effects of miRNA-21 on PTEN/PI3K/Akt/HIF-1? pathway were also assessed using western blotting. To further evaluate the roles of miRNA-21 in osteogenesis in vivo, we conducted animal experiments in rat and canine. New bone formation was assessed using micro-CT and histological methods. RESULTS:In the present study, we found that miRNA-21 promotes the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro. Using gain- and loss-of-function studies, we found that miRNA-21 promoted the osteogenic ability of BMSCs by increasing P-Akt and HIF-1? activation. Finally, we verified the essential role of miRNA-21 in osteogenesis by implanting a miRNA-21-modified BMSCs/?-tricalcium phosphate (?-TCP) composite into critical size defects. Radiography, micro-CT, and histology revealed significantly greater volume of new bone formation in the miRNA-21 group than in the control group. CONCLUSION:In conclusion, our study demonstrated an essential role of miRNA-21 in promoting maxillofacial bone regeneration via the PTEN/PI3K/Akt/HIF-1? pathway.

SUBMITTER: Yang C 

PROVIDER: S-EPMC6387542 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects.

Yang Chi C   Liu Xiaohan X   Zhao Kai K   Zhu Youming Y   Hu Bin B   Zhou Yong Y   Wang Mohan M   Wu Yiqun Y   Zhang Chengfei C   Xu Jianguang J   Ning Yujie Y   Zou Duohong D  

Stem cell research & therapy 20190222 1


<h4>Background</h4>Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge. Many studies have emphasized the osteogenic and angiopoietic abilities of stem cells for tissue regeneration. We previously showed that microRNA-21 (miRNA-21) can promote angiogenesis in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). In the present study, the role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated  ...[more]

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