Titanium With Nanotopography Induces Osteoblast Differentiation by Regulating Endogenous Bone Morphogenetic Protein Expression and Signaling Pathway

Abstract

We aimed at evaluating the effect of titanium (Ti) with nanotopography (Nano) on the endogenous expression of BMP-2 and BMP-4 and the relevance of this process to the nanotopography-induced osteoblast differentiation. MC3T3-E1 cells were grown on Nano and machined (Machined) Ti surfaces and the endogenous BMP-2/4 expression and the effect of BMP receptor BMPR1A silencing in both osteoblast differentiation and expression of genes related to TGF-β/BMP signaling were evaluated. Nano supported higher BMP-2 gene and protein expression and upregulated the osteoblast differentiation compared with Machined Ti surface. The BMPR1A silencing inhibited the osteogenic potential induced by Nano Ti surface as indicated by reduced alkaline phosphatase (ALP), osteocalcin and RUNX2 gene expression, RUNX2 protein expression and ALP activity. In addition, the expression of genes related to TGF-β/BMP signaling was deeply affected by BMPR1A-silenced cells grown on Nano Ti surface. In conclusion, we have demonstrated for the first time that nanotopography induces osteoblast differentiation, at least in part, by upregulating the endogenous production of BMP-2 and modulating BMP signaling pathway. J. Cell. Biochem. 117: 1718-1726, 2016. © 2015 Wiley Periodicals, Inc.

The effect of collagen coating on titanium with nanotopography on in vitro osteogenesis

“…These results lend support to our initial hypothesis that collagen coating of nanotopographic Ti surface enhances in vitro osteogenesis, which could be due to increasing and/or accelerating osteoblast differentiation as showed for already differentiated osteoblasts as well as inducing osteoblast differentiation under nonosteogenic conditions . Considering that nanotopography increases the endogenous production of BMP‐2 and that collagen interacts with integrin receptors to regulate osteoblast differentiation induced by BMP‐2, it is possible to suggest that the synergic positive effect of nanotopography and collagen coating on in vitro osteogenesis observed here is, at least in part, modulated by BMP‐2 signaling pathway …”

Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography

“…The osseoinductive capacity makes this nanotopography an appealing model of investigation of the signaling pathways triggered by an osteogenic microenvironment that drive the process of osseointegration . In this context, we have already shown that this surface regulates several cell machinery components, including integrins, in order to induce osteoblast differentiation …”

The Role of Titanium Surface Nanostructuring on Preosteoblast Morphology, Adhesion, and Migration

“…In the studies [34,35] the nanotopography-induced osteogenic differentiation of the MC3T3-E1 cells is addressed. The corresponding analysis of the samples was performed at day 7 and day 4, respectively.…”

“…The papers of Karazisis et al [37] and Freitas et al [38] present the effect of Ti nanotopography on bone response by using the same method as Castro-Raucci et al [34] and Kato et al, [35] however applying an in vivo approach. The publication history of the articles [34,35] indicates that the studies are performed in a logical order: from in vitro to in vivo.…”

“…The publication history of the articles [34,35] indicates that the studies are performed in a logical order: from in vitro to in vivo. We consider our research as a comprehensive study, investigating (i) cell response to the mesoporous titania (TMS) fabricated by the novel sonochemical treatment, and (ii) comparison between the cell responses to ordered and disordered surface nanotopography.…”