title: Pro-osteogenic topographical cues promote early activation of osteoprogenitor differentiation via enhanced TGFβ, Wnt, and Notch signaling.
abstract: OBJECTIVE
  Titanium implant surfaces with modified topographies have improved osteogenic properties in vivo. However, the molecular mechanisms remain obscure. This study explored the signaling pathways responsible for the pro-osteogenic properties of micro-roughened (SLA) and chemically/nanostructurally (modSLA) modified titanium surfaces on human alveolar bone-derived osteoprogenitor cells (BCs) in vitro.
  
  
  METHODS
  The activation of stem cell signaling pathways (TGFβ/BMP, Wnt, FGF, Hedgehog, Notch) was investigated following early exposure (24 and 72 h) of BCs to SLA and modSLA surfaces in the absence of osteogenic cell culture supplements.
  
  
  RESULTS
  Key regulatory genes from the TGFβ/BMP (TGFBR2, BMPR2, BMPR1B, ACVR1B, SMAD1, SMAD5), Wnt (Wnt/β-catenin and Wnt/Ca(2+) ) (FZD1, FZD3, FZD5, LRP5, NFATC1, NFATC2, NFATC4, PYGO2, LEF1) and Notch (NOTCH1, NOTCH2, NOTCH4, PSEN1, PSEN2, PSENEN) pathways were upregulated on the modified surfaces. These findings correlated with a higher expression of osteogenic markers bone sialoprotein (IBSP) and osteocalcin (BGLAP), and bone differentiation factors BMP2, BMP6, and GDF15, as observed on the modified surfaces.
  
  
  CONCLUSIONS
  These findings demonstrate that the activation of the pro-osteogenic cell signaling pathways by modSLA and SLA surfaces leads to enhanced osteogenic differentiation as evidenced after 7 and 14 days culture in osteogenic media and provides a mechanistic insight into the superior osseointegration on the modified surfaces observed in vivo.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia.
authors.forename: Nishant
authors.initials: N
authors.lastname: Chakravorty
authors.forename: Stephen
authors.initials: S
authors.lastname: Hamlet
authors.forename: Anjali
authors.initials: A
authors.lastname: Jaiprakash
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.forename: Adekunle
authors.initials: A
authors.lastname: Oloyede
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alfarsi
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
authors.forename: Saso
authors.initials: S
authors.lastname: Ivanovski
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003463:Cues; D020869:Gene Expression Profiling; D055436:Growth Differentiation Factor 15 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties; D014025:Titanium; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D051880:Receptors, Notch; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D015675:Osteocalcin; D014025:Titanium
keywords: cell signaling; osteoprogenitor differentiation; titanium surface modification; topography