Enhanced osteogenic differentiation of rat bone marrow mesenchymal stem cells on titanium substrates by inhibiting Notch3 |
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| Affiliation: | 1. Department of Oral and Maxillofacial Surgery, Stomatology Hospital, School of Medical, Zhejiang University, Yan’an Road, Hangzhou, PR China;2. Department of Implantology, Stomatology Hospital, School of Medical, Zhejiang University, Yan’an Road, Hangzhou, PR China;3. Department of Oral Medicine, Stomatology Hospital, School of Medical, Zhejiang University, Yan’an Road, Hangzhou, PR China;1. Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA;1. Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy;2. Department of Pediatric Surgery, Catania University, Catania, Italy;3. Department of Pediatric Surgery, Medical University of Jena, Jena, Germany;4. Department of Pediatric Surgery, Wrocław Medical University, Wrocław, Poland;5. Department of Pediatric Surgery, Chelsea and Westminster Children Hospital, London, UK;6. Department of Pediatric Surgery, Hôpital de Bicetre, Paris, France;1. Ministry of Education, Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China;2. Department of Cardiothoracic Surgery, Children''s Hospital of Chongqing Medical University, Chongqing, China;3. Renal Department and Nephrology Institute, Sichuan Provincial People''s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China;3. From the Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, Scotland, United Kingdom;4. the Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, Oulu Center for Cell Matrix Research, University of Oulu, FIN-90014 Oulu, Finland;1. Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA |
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| Abstract: | ![]()
ObjectiveThe role of the Notch pathway has already been identified as a crucial regulator of bone development. However, the Notch signaling pathway has gone largely unexplored during osseointegration. This study aims to investigate the role of Notch signaling on osteogenic differentiation of rat derived bone marrow mesenchymal stem cells (BMSCs) on sandblasted, large-grit, acid-etched (SLA) treated Ti disks.MethodsThe involved target genes in Notch pathways were identified by in vitro microarray and bioinformatics analyses with or without osteogenic induction. Adhesion, proliferation, and osteogenic related assay were subsequently conducted with target gene shRNA treatment.ResultsWe found that 11 genes in the Notch signaling pathway were differentially expressed after osteogenic induction on SLA-treated Ti disks, which included up-regulated genes (Notch2, Dll1, Dll3, Ncstn, Ncor2, and Hes5) and down-regulated genes (Notch3, Lfng, Mfng, Jag2 and Maml2). With Notch3 shRNA treatment, the adhesion and proliferation of BMSCs on SLA-treated Ti disks were inhibited. Moreover, the expression levels of alkaline phosphatase (ALP), osteocalcin (OCN), calcium deposition, BMP2 and Runx2 increased significantly compared with that observed in control groups, suggesting that the function of Notch3 was inhibitory in the osteogenic differentiation of BMSCs on SLA-treated titanium.ConclusionsInhibition Notch3 can enhance osteogenic differentiation of BMSCs on SLA-treated Ti disks, which potentially provides a gene target for improving osseointegration. |
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| Keywords: | Notch3 Bone marrow mesenchymal stem cells (BMSCs) Titanium Osteogenic differentiation |
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