Effects of Bone Morphogenetic Proteins on Osteoblast Cells: Vascular Endothelial Growth Factor, Calcium, Inorganic Phosphate, and Nitric Oxide Levels
ABSTRACT Bone morphogenetic proteins (BMPs) play an important role in the initiation of bone formation by affecting cell growth and differentiation in a variety of cell types including osteoblasts. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vasculogenesis, and also, VEGF signaling is important for skeletal development. Nitric oxide (NO), calcium (Ca), and inorganic Phosphate (Pi) are important molecules for cell functions. In this study, the effects of BMP on VEGF, Ca, NO, and Pi levels were investigated in an osteoblast cell culture.
Fifty thousand cells per milliliter were seeded and cultured on graft materials for 24 and 48 hours. Different concentrations of BMPs (combination of BMPs numbered from 1 to 14) were supplemented to the medium.
BMP was found to increase VEGF (P = 0.00), Ca (P = 0.02), and Pi (P = 0.00) especially in the first 24 hours. The increase in the NO in the experimental groups were found to be statistically insignificant (P = 0.12).
Our data state that further investigation should be performed on the effects of BMPs on osteoblast cell membranes and membrane receptors and cell signaling, together with their known effects on early phases of bone and vascular epithelial tissue formation.
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ABSTRACT: BACKGROUND: Vascular endothelial cells can promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which provide nutrition supports for osteogenic differentiation of stem cells. OBJECTIVE: To investigate the effects of human umbilical vein endothelial cells (HUVECs) on the morphology, growth, differentiation of BMSCs as well as the runt-related transcription factor 2 (Runx2) gene expression in a co-cultivation system. METHODS: In a co-cultivation system, passage 3 BMSCs and passage 3 HUVECs were cultured together and served as experimental group. Passage 3 BMSCs were simply cultured and served as control group. At 4, 6, 10 days of culture, BMSCs morphology, alkaline phosphatase activity and Runx2 gene expression were determined. RESULTS AND CONCLUSION: Compared with control group, BMSCs morphology was diverse, and cell conjunction and fusion appeared, and osteogenic differentiation was obvious during anaphase in the experimental group. At each time point, there was no obvious change in alkaline phosphatase activity in the control group, and alkaline phosphatase activity was significantly higher in the experimental group than in the control group (P < 0.05). At 6 and 8 days, Runx2 gene expression in the experimental group was about 4 times that in the control group (P < 0.01). This suggests that in the co-cultivation system, intravenous endothelial cells can promote Runx2 expression in BMSCs and induce osteogenic differentiation of BMSCs. Yang RN, Liu L, Wang FK, Zhao DP. Effects of vascular endothelial cells on runt-related transcription factor 2 expression and osteogenic differentiation of bone marrow mesenchymal stem cells in a co-cultivation system.Zhongguo Zuzhi Gongcheng Yanjiu.
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ABSTRACT: Bone marrow mesenchymal stem cells (BMMSCs) are multipotent stem cells that can differentiate into different blastoderm cells in vitro. In this study, BMMSCs in rabbit bone marrow were isolated by density gradient centrifuge separation, purified and expanded in vitro. BMP-2 and FGF 2 were used for differentiation into osteoblasts, and the results demonstrated that bone morphogenetic proteins (BMPs) could affect the differential direction of the BMMSCs. PCR assays indicated that BMP signals pathway played important roles in osteoblasts differentiation of BMMSCs, and the members included BMPRI, Smad 1, Smad 5, Smad 8, Runx 2, collage type I and osteopontin. This study provides a theoretical basis and experimental evidence for the therapeutic application of BMMSCs to the treatment of bone injury.01/2013; DOI:10.3109/10731199.2012.731412
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ABSTRACT: In total hip arthroplasty, wear particles generated at articulating surfaces and interfaces between bone, cement and implants have a negative impact on osteoblasts, leading to osteolysis and implant loosening. The aim of this experimental study was to determine the effects of particulate wear debris generated at the interface between straight stainless steel hip stems (Exeter®) and three different bone cements (Palacos® R, Simplex™ P and Cemex® Genta) on cell viability, collagen synthesis and cytokine expression in human osteoblasts. Primary osteoblasts were treated with various concentrations of wear particles. The synthesis of procollagen type I and different cytokines was analysed, and markers for apoptosis and necrosis were also detected. The cytokine synthesis rates in the osteoblasts were initially increased and varied, depending on incubation time and particle concentration. Specific differences in the synthesis rates of interleukin (IL)‑6, IL-8, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) were observed with the different bone cements examined. The negative effect of the particles on the synthesis of procollagen type I and increased rates of cell apoptosis and necrosis were observed with all three cements analysed. Our present data suggest that wear particles from the interface between the total hip stem and bone cement have a significant effect on viability, cytokine expression and collagen synthesis in human osteoblasts, depending on the bone cement used.International Journal of Molecular Medicine 05/2013; 32(1). DOI:10.3892/ijmm.2013.1383