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Clin Oral Implants Res. 2014 Apr;25(4):475-86. doi: 10.1111/clr.12178. Epub 2013 Apr 21.

Pro-osteogenic topographical cues promote early activation of osteoprogenitor differentiation via enhanced TGFβ, Wnt, and Notch signaling.

Author information

1
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia.

Abstract

OBJECTIVES:

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.

MATERIALS AND 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.

KEYWORDS:

cell signaling; osteoprogenitor differentiation; titanium surface modification; topography

PMID:
23600707
DOI:
10.1111/clr.12178
[Indexed for MEDLINE]

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