Background: Sand-blasted, large grit, acid etched (SLA) and modSLA (hydrophilic SLA) titanium implant surfaces are recognized to have improved osseointegration and osteogenic properties. These properties are guided by activation of several molecular signaling pathways. This study explored the signaling pathways activated following early exposure (24 h) of osteoprogenitor cells to modSLA and SLA surfaces and their possible regulation by microRNAs. Materials and methods: Human osteoprogenitor cells were cultured on modSLA, SLA and smooth (SMO) surfaces. The relative expression of key genes involved in signaling pathways, and miRNAs related to cell development and differentiation was evaluated. Target predictions for the differentially regulated miRNAs were performed using TargetScan and sorted for genes of TGFb/BMP and Wnt/Ca2+ pathways (for downregulated miRNAs) and inhibitors of osteogenesis (for upregulated miRNAs). Results: The study confirmed that TGFb/BMP, Wnt/Ca2+ and Notch pathways are activated within 24 h of exposure to modified surfaces. Several miRNAs showed differential expression on modSLA and SLA surfaces. Target predictions for the down-regulated miRNAs revealed several potential genes of the TGFb/BMP and Wnt/Ca2+ pathways as potential targets. Conclusion: This study demonstrated that modified titanium surfaces induce differential regulation of miRNAs that potentially regulate the TGFb/BMP andWnt/Ca2+ pathways leading to improved osteogenicity