The main objective of this study was to compare the response of bone progenitor cells (D1) to silica-based calcium phosphate glass (80:15:5) powders prepared by sol–gel template-free (SCP) and template-structured (SCP-T) processes. The SCP-T powders exhibited an approximately three times larger specific surface area compared to that of SCP powders. The formation of a hysteresis loop also signified the presence of mesoporous structures in the SCP-T samples; however, a hysteresis loop was not observed for the SCP samples, resulting in 1/5 of the pore volume of the SCP-T samples. The viability of the cells cultured in media containing the SCP-T powders for 24, 48, and 72h was greater than 90%. D1 cells cultured on SCP and SCP-T substrates showed the highest cell proliferation after 1h of culture. The number of cells decreased from 24h to 168h for all experimental groups (p>0.05). Importantly, both the SCP and SCP-T substrates had positive effects on the osteogenic differentiation and mineralization of the progenitor cells. However, cells cultured on SCP-T had approximately 3.4 times higher ALP activity.