Identification of Early Response Genes to Roughness and Fluoride Modification of Titanium Implants in Human Osteoblasts

Abstract
Purpose: Tissue response after implantation determines the success of the healing process. This response is not only dependent on the chemical properties of the implant surface but also by the surface topography or its roughness. Although in vitro and in vivo studies show improved results with rough- and fluoride-modified implants, the mechanisms behind these findings are still unknown. Methods and Materials: Here, we have used a two-step procedure to identify novel genes related to the early response of primary human osteoblasts to roughness and fluoride-modified titanium implants. Results: Two hundred seventeen genes responding to roughness were identified by microarray analysis and 198 genes responding to fluoride, 33 genes were common. Those identified genes related to bone and mineralization were further investigated by real-time reverse-transcriptase polymerase chain reaction. After 1 day of culture, toll-like receptor 3, ankylosis-progressive homolog, decorin, osteocalcin, and runt-related transcription factor-2 were classified as responsive genes to roughness; Distal-less homeobox-2 and Tuftelin-1 as responsive genes to fluoride treatment. Responsive genes to both treatments were collagen type I, parathyroid hormone-like hormone, hairy and enhancer of split-1, follistatin, ectonucleotide pyrophosphatase/phosphodiesterase-1, and thyroid hormone receptor-alpha. Conclusion: Our strategy was useful for identifying novel genes that might be involved in the early response of osteoblasts to rough and fluoride-modified titanium implants.