Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties

• Published in: Journal of cellular biochemistry Vol. 120; no. 4; pp. 6555 - 6569
• Main Authors: Carvalho, Marta S, Cabral, Joaquim MS, da Silva, Cláudia L, Vashishth, Deepak
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-04-2019
• Subjects: Alkaline phosphatase; Angiogenesis; Biocompatibility; Biomedical materials; Bone growth; Bone marrow; Bone matrix; Calcium; Calcium (extracellular); Capillary tubes; Cell adhesion & migration; Cell growth; Cell migration; Cell proliferation; Differentiation (biology); Endothelial cells; Grafts; human bone marrow mesenchymal stem/stromal cells; human umbilical vein endothelial cells; Life expectancy; Life span; Long bone; Mesenchyme; Mineralization; mRNA; Osteoblastogenesis; Osteoblasts; Osteocalcin; Osteogenesis; Osteopontin; Physiological effects; Properties (attributes); Proteins; Regeneration; Regeneration (physiology); Ribonucleic acid; RNA; Skin & tissue grafts; Stem cells; Stromal cells; Substitute bone; Supplements; Synergistic effect; Umbilical vein; osteocalcin; human bone marrow mesenchymal stem/stromal cells; osteogenesis; angiogenesis; osteopontin; human umbilical vein endothelial cells
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27948

A high demand for functional bone grafts is being observed worldwide, especially due to the increased life expectancy. Osteoinductive components should be incorporated into functional bone grafts, accelerating cell recruitment, cell proliferation, angiogenesis, and new bone formation at a defect site. Noncollagenous 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. Therefore, we assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells (hBM MSC) proliferation and osteogenic differentiation. OPN dose‐dependently increased the proliferation of hBM MSC, as well as improved the angiogenic properties of human umbilical vein endothelial cells (HUVEC) by increasing the capillary‐like tube formation in vitro. On the other hand, OC enhanced the differentiation of hBM MSC into osteoblasts and demonstrated an increase in extracellular calcium levels and alkaline phosphatase activity, as well as higher messenger RNA levels of mature osteogenic markers osteopontin and osteocalcin. In vivo assessment of OC/OPN‐enhanced scaffolds in a critical‐sized defect rabbit long‐bone model revealed no infection, while new bone was being formed. Taken together, 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.
Noncollagenous 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, and angiogenesis are still undefined. In this study, we reported that OPN dose‐dependently increased the proliferation of human bone marrow mesenchymal stem/stromal cells (hBM MSC), as well as improved angiogenic potential, while OC enhanced the differentiation of hBM MSC into osteoblasts.