title: Enhanced osteogenic differentiation of rat bone marrow mesenchymal stem cells on titanium substrates by inhibiting Notch3.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Inhibition Notch3 can enhance osteogenic differentiation of BMSCs on SLA-treated Ti disks, which potentially provides a gene target for improving osseointegration.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Stomatology Hospital, School of Medical, Zhejiang University, Yan'an Road, Hangzhou, PR China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Implantology, Stomatology Hospital, School of Medical, Zhejiang University, Yan'an Road, Hangzhou, PR China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Implantology, Stomatology Hospital, School of Medical, Zhejiang University, Yan'an Road, Hangzhou, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Stomatology Hospital, School of Medical, Zhejiang University, Yan'an Road, Hangzhou, PR China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Oral Medicine, Stomatology Hospital, School of Medical, Zhejiang University, Yan'an Road, Hangzhou, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Implantology, Stomatology Hospital, School of Medical, Zhejiang University, Yan'an Road, Hangzhou, PR China. Electronic address: guo_li1977@aliyun.com.
authors.forename: Guoli
authors.initials: G
authors.lastname: Yang
mesh_terms: D000134:Acid Etching, Dental; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002113:Calcification, Physiologic; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D046228:Microarray Analysis; D008855:Microscopy, Electron, Scanning; D015675:Osteocalcin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000071656:Receptor, Notch3 / Q000037:antagonists & inhibitors*; D013499:Surface Properties; D014025:Titanium
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D050657:Core Binding Factor alpha Subunits; C498556:Notch3 protein, rat; D000071656:Receptor, Notch3; D015675:Osteocalcin; D014025:Titanium; D000469:Alkaline Phosphatase
keywords: Bone marrow mesenchymal stem cells (BMSCs); Notch3; Osteogenic differentiation; Titanium