There is a high demand for functional bone grafts worldwide partly due to the increased life expectancy. Bone matrix proteins, especially osteopontin (OPN) and osteocalcin (OC), have been reported to regulate some physiological process, such as cell migration and bone mineralization. However, the effects of OPN and OC on cell proliferation, osteogenic differentiation, mineralization and angiogenesis are still undefined. In a recent study published in Journal of Cellular and Biochemistry, researchers from SCERG-iBB working with colleagues from the Rensselaer Polytechnic Institute assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells proliferation and osteogenic differentiation. These results suggest that OC and OPN stimulate bone regeneration by inducing stem cell proliferation, osteogenesis and by enhancing angiogenic properties. The synergistic effect of OC and OPN observed in this study can be applied as an attractive strategy for bone regeneration therapeutics by targeting different vital cellular processes.