Abstract
BackgroundFunctional 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.MethodsWestern 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-1α 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.ResultsIn 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-1α activation. Finally, we verified the essential role of miRNA-21 in osteogenesis by implanting a miRNA-21-modified BMSCs/β-tricalcium phosphate (β-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.ConclusionIn conclusion, our study demonstrated an essential role of miRNA-21 in promoting maxillofacial bone regeneration via the PTEN/PI3K/Akt/HIF-1α pathway.
Highlights
Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge
Expression of osteogenic- and angiogenic-related genes in miRNA-21-modified bone marrow-derived stem cells (BMSCs) To assess the expression levels of osteogenic mRNAs, BMSCs were infected with Lenti-miRNA-21, and qPCR was performed at 0, 1, 4, 7, 14, and 21 days after transfection (Fig. 1)
It was revealed that hypoxia-inducible factor-1α (HIF-1α) and VEGF mRNA levels were upregulated at 4 days after Lenti-miRNA-21 infection
Summary
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. The role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated. The maxillofacial bone is an important anatomical component of craniofacial function and morphology [1]. Various factors including congenital malformation, trauma, and tumors can lead to maxillofacial bone defects. In such cases, functional maxillofacial bone reconstruction is complex and difficult. Tissue engineering has gradually become one of the promising alternatives to traditional bone regeneration techniques
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