Receptor Kinase AXL is Modulated in the Osteogenic Differentiation of Human Mesenchymal Stromal Cells on Modified Titanium Implant SurfacesMohammad Ramine Khan1, Nikolaos Donos2,3, Vehid Salih2,4 and Peter Mark Brett2*
- *Corresponding Author:
- Dr Peter Mark Brett
Biomaterials and Tissue Engineering
UCL, Eastman Dental Institute
University College London, 256 Grays’s Inn Road
London WC1X 8LD, United Kingdom
Tel: 0044 (0)203 456 1104
Fax: 0044 (0)203 456 1104
E-mail: [email protected]
Received date: August 07, 2014; Accepted date: September 12, 2014; Published date: September 14, 2014
Citation: Khan MR, Donos N, Salih V, Brett PM (2014) Receptor Kinase AXL is Modulated in the Osteogenic Differentiation of Human Mesenchymal Stromal Cells on Modified Titanium Implant Surfaces. J Stem Cell Res Ther 4:233. doi:10.4172/2157-7633.1000233
Copyright: © 2014 Khan MR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Titanium (Ti) implants with micro-rough topography and high surface free energy promote osseointegration, which in vitro analyses suggest is due to a novel enhancement in cellular osteogenic differentiation and function. The AXL receptor tyrosine kinase (AXL) is expressed on mesenchymal stromal cells (MSCs) and is implicated with its ligand, Growth arrest-specific 6 (GAS6), in the negative regulation of osteogenic differentiation, and may be modulated in the enhanced osteogenic differentiation of MSCs on modified Ti surfaces. This hypothesis was tested by culturing human MSCs on tissue culture plastic (TCP), polished (P), micro-rough-hydrophobic (SLA) and micro-rough hydrophilic (modSLA) Ti surfaces for seven days. Total RNA and protein levels of AXL and GAS6 were examined by real time PCR and ELISA, respectively. The effects of deregulating the signalling pathway in hMSCs with either receptor agonist or antagonist were investigated by analysing calcium mineralisation and soluble osteoblastic marker synthesis. The MSCs were found to significantly down-regulate AXL and GAS6 earlier on rough surfaces compared to smooth over seven days. Addition of the receptor agonist caused a relative decrease in calcium mineralisation that was most marked for TCP compared to any Ti surface. The antagonist did not affect mineralisation but caused a relative increase in osteoblastic soluble protein levels on rough surfaces only. Gene expression data showed an up-regulation of RUNX2 and beta-catenin with the receptor antagonist. These findings suggest that a down-regulation of AXL correlates with increased cellular mineralisation on the modified surfaces and that it might be a putative biomarker for assessing the clinical efficacy of endosseous implants.