Osteoporosis is a degenerative bone disorder that affects millions of people worldwide. Despite many novel drugs or therapy strategies that have been developed, the curative effect of current treatments is far from satisfying. Development of effective treatments toward osteoporosis is imminent. Bone mesenchymal stem cells (BMSCs) are one kind of pluripotent stem cells, which are not only easy to separate and purify but also can self-renew and differentiate into osteogenic cells. In this work, a traceable drug delivery system based on gadolinium-labeled defect-related luminescent mesoporous silica nanoparticles (MSNs) was developed for bone marrow homing and enhanced osteogenic differentiation. The results showed that dexamethasone (DEX) could be loaded into nanocarriers and gave a sustained release behaviour. A unique defect-related luminescent property could be utilized to monitor the drug release effectively. In addition, the nanocarriers showed good biocompatibility and were uptaken mainly via an energy-dependent endocytosis process which was mediated by the macropinocytosis pathway. Furthermore, the nanocarriers can be simultaneously used as predominant contrast agents for magnetic resonance imaging. More importantly, DEX-loaded nanocarriers can significantly enhance the alkaline phosphatase activity and promote formation of matrix nodules of the BMSCs.