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Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation

Regenerative Biomaterials 2021年第2期8卷 34-42页

作者： Rena Shido Yoshinori Sumita Masahito Hara mayumi iwatake Shun Narahara mayumi Umebayashi Kei-ichiro Miura Yukinobu Kodama Izumi Asahina Department of Regenerative Oral Surgery Unit of Translational MedicineNagasaki University Graduate School of Biomedical Sciences1-7-1 SakamotoNagasaki 852-8588Japan Basic&Translational Research Center for Hard Tissue Disease Unit of Translational MedicineNagasaki University Graduate School of Biomedical Sciences1-7-1 SakamotoNagasaki 852-8588Japan Laboratory of Craniofacial Tissue Engineering and Stem Cells Faculty of DentistryMcGill University3640 University StreetM43MontrealQuebec H3A 2B2Canada Department of Hospital Pharmacy Nagasaki University Hospital1-7-1 SakamotoNagasaki 852-8501Japan

Gene-activated matrix(GAM)has a potential usefulness in bone engineering as an alternate strategy for the lasting release of osteogenic proteins but efficient methods to generate non-viral GAM remain to be *** this study,we investigated whether an atelocollagen-based GAM containing naked-plasmid(p)DNAs encoding microRNA(miR)20a,which may promote osteogenesis in vivo via multiple pathways associated with the osteogenic differentiation of mesenchymal stem/progenitor cells(MSCs),facilitates rat cranial bone ***,we confirmed the osteoblastic differentiation functions of generated pDNA encoding miR20a(pmiR20a)in vitro,and its transfection regulated the expression of several of target genes,such as Bambi1 and PPARc,in rat bone marrow MSCs and induced the increased expression of ***,when GAMs fabricated by mixing 100 ll of 2%bovine atelocollagen,20mg b-TCP granules and 0.5mg(3.3 lg/ll)AcGFP plasmid-vectors encoding miR20a were transplanted to rat cranial bone surface,the promoted vertical bone augmentation was clearly recognized up to 8 weeks after transplantation,as were upregulation of VEGFs and BMP4 expressions at the early stages of ***,GAM-based miR delivery may provide an alternative non-viral approach by improving transgene efficacy via a small sequence that can regulate the multiple pathways.

关键词： gene-activated matrix in vivo gene transfer bone augmentation atelocollagen mir20a

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