Abstract
Understanding the biocomplexity of cell behavior in relation to the topographical characteristics of implants is essential for successful osseointegration with good longevity and minimum failure. Here, we investigated whether culture on titanium oxide (TiO2) nanotubes of various diameters could affect the behavior and differentiation of MC3T3-E1 cells. Among the tested nanotubes, those of 50 nm in diameter were found to trigger the expression of the osteoblast-specific transcription factors, sp7 and Dlx5, and upregulate the expression of alkaline phosphatase (ALP). Here, we report that miR-488 was significantly induced in osteoblasts cultured on 50 nm nanotubes and continued to increase with the progression of osteoblast differentiation. Furthermore, downregulation of miR-488 suppressed the expression levels of ALP and matrix metalloprotease-2 (MMP-2). This suppression of ALP transcription was overcome by treatment with the MMP-2 activator, bafilomycin A1. Collectively, these results suggest that 50 nm is the optimum TiO2nanotube diameter for implants, and that modulation of miR-488 can change the differentiation activity of cells on TiO2nanotubes. This emphasizes that we must fully understand the physicochemical properties of TiO2nanotubes and the endogenous biomolecules that interact with such surfaces, in order to fully support their clinical application.
Highlights
Accumulating experimental evidence suggests that nanoscale topography is an important factor for cellular recognition of the biological microenvironment and biomimetic materials used for vascular grafts, stents, and bone implants [1, 2]
We previously showed that miR-488 is involved in regulating matrix metalloprotease-2 (MMP-2) during endochondral ossification [13], indicating that miR-488 is involved in bone formation
One of the biggest challenges in developing implants with improved longevity and minimum failure is the control of successful osseointegration
Summary
Accumulating experimental evidence suggests that nanoscale topography is an important factor for cellular recognition of the biological microenvironment and biomimetic materials used for vascular grafts, stents, and bone implants [1, 2]. Several studies have suggested that some cells can show cell-type-specific behaviors and activities on TiO2 nanotubes. Mesenchymal stem cells showed enhanced activity on anatase-phase nanotubes (70–100 nm diameter), and proliferation of smooth muscle cells was enhanced on TiO2 [4]. Since MMP-2 is thought to control homeostatic and morphogenetic events during osteogenic differentiation [15], we speculate that miR488 is involved in the formation of bone [14, 16]. We studied the in vitro behavior of osteoblast cells cultured on vertically aligned TiO2 nanotubes of different diameters. We investigated the effect of such nanostructures on osteoblast cell morphology and the kinetics of cell proliferation, examined cell responses on nanotubes versus plastic polypyrene layers, and tested for differential expression of miR-488
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
