Integrin α5 controls osteoblastic proliferation and differentiation responses to titanium substrates presenting different roughness characteristics in a roughness independent manner

B. G. Keselowsky, L. Wang, Z. Schwartz, A. J. Garcia, B. D. Boyan

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Integrin α5β1 regulates osteoblast proliferation and differentiation on smooth synthetic surfaces presenting different chemistries, but it is not known whether this integrin controls osteoblast behavior on surfaces that have micron-scale rough topographies. We cultured MG63 human osteoblast-like cells on titanium substrates with three different roughness characteristics: chemically polished (PT), grit blasted and acid etched with a complex topography consisting of 20-100 μm craters and 0.5-2 μm micropits (SLA), and plasma-sprayed Ti with irregular projections (TPS). Cells spread well on PT but displayed a smaller footprint on SLA or TPS. Nuclei were larger on PT as well. α5β1 binding and FAK phosphorylation were greater on the rougher surfaces (TPS > SLA > PT). Antibodies against the α5β1 binding site on fibronectin had no effect on cell number at 3 days, but [3H]- thymidine incorporation was increased, suggesting that binding to fibronectin was necessary for cell cycle regulation. Antibodies to the α5 subunit reduced cell number at 3 days on PT and TPS and reduced DNA synthesis on all substrates in a surface microstructure-independent manner. At 7 days, cell numbers were reduced on PT, and DNA synthesis was reduced by 50% on all surfaces. At 7 days, anti-α5 antibodies caused a partial reduction in alkaline phosphatase enzyme activity on all surfaces, but this effect was independent of surface microstructure. These results indicate that surface micron-scale topography modulates α5β1 integrin binding and FAK activation. Signaling via α5-dependent mechanisms is required for DNA synthesis and regulation of alkaline phosphatase, but this effect is independent of surface microstructure.

Original languageEnglish (US)
Pages (from-to)700-710
Number of pages11
JournalJournal of Biomedical Materials Research - Part A
Volume80
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • FAK activation
  • Fibronectin binding
  • Integrin α
  • MG63 cells
  • Osteoblasts
  • Surface microarchitecture
  • Titanium

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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