Substitution of mesoporous bioactive glass nanoparticles (MBGNs; composition in mol%: 70 SiO2- 30 CaO) with therapeutically active ions such as Molybdenum (Mo) ions modulates their osteogenic properties. To overcome the limited pro-angiogenic capability of MBGNs, a combination of Mo with pro-angiogenic boron (B) has been suggested. With regard to the missing knowledge about the global cellular response of bone marrow-derived human mesenchymal stromal cells (BMSCs) exposed to B- and Mo-MBGNs and their combinations, in this work a whole genome expression profiling was conducted to identify differentially expressed genes (DEGs) in BMSCs exposed to MBGNs, B-MBGNs, Mo-MBGNs and their combinations. Results were compared to those on untreated BMSCs. In MBGNs-exposed BMSCs, 93 DEGs were identified. Reactome pathway analysis revealed an overrepresentation of genes coding for enzymes of the cholesterol biosynthesis in all MBGNs-treated groups, whereas genes coding for molecules of extracellular matrix (ECM) proteoglycans and signaling of transforming growth factor-beta (TGF-β) family members were overrepresented after exposure to Mo-MBGNs. The DEGs of the identified Reactome pathways are tightly involved in modulating osteogenic differentiation. Further research is needed to clarify the exact role of the identified genes on the osteogenic potency of ion-substituted MBGNs adding fundamental information for the application of such nanoparticles in ionic medicine approaches.