Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) are dominant seed cell sources for bone regeneration. Bone morphogenetic proteins (BMPs) initiate cartilage and bone formation in a sequential cascade. Vascular endothelial growth factor (VEGF) is an essential coordinator of extracellular matrix remodeling, angiogenesis and bone formation. In the present study, the effects of the vascular endothelial growth factor 165 (VEGF165) and bone morphogenetic protein 2 (BMP2) genes on bone regeneration were investigated by the lentivirus-mediated cotransfection of the two genes into rat bone marrow-derived MSCs. The successful co-expression of the two genes in the MSCs was confirmed using quantitative polymerase chain reaction (qPCR) and western blot analysis. The results of alizarin red and alkaline phosphatase (ALP) staining at 14 days subsequent to transfection showed that the area of staining in cells transfected with BMP2 alone was higher than that in cells transfected with BMP2 and VEGF165 or untransfected control cells, while the BMP2 + VEGF165 group showed significantly more staining than the untransfected control. This indicated that BMP2 alone exhibited a stronger effect in bone regeneration than BMP2 in combination with VEGF165. Similarly, in inducing culture medium, the ALP activity of the BMP2 + VEGF165 group was notably suppressed compared with that of the BMP2 group. The overexpression of VEGF165 inhibited BMP2-induced MSC differentiation and osteogenesis in vitro. Whether or not local VEGF gene therapy is likely to affect bone regeneration in vivo requires further investigation.

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine

“…What is interesting is that the HIF-1α gene overexpression alone enhanced the osteogenic differentiation of BM-MSCs just as well [115]. Similar results were reported in the double Ang-1/BMP-2 and VEGF/BMP-2-overexpressing BM-MSCs [47, [116][117][118]. However, BM-MSCs engineered to exclusively overexpress the pro-angiogenic VEGF gene were found to be strong inducers of new bone formation by the promotion of new vessel formation among the scaffolds used as templates [119,120].…”

“…GDF-5 [102][103][104] TIMP-1 [106] Bcl-2 [101] BONE FORMATION BMP-2 [86][109-111] BMP-2/SDF-1β [113] BMP-2/HIF-1α [114] BMP-2/Ang-1 [47] BMP-2/VEGF [116][117][118] BMP-2/miR-148b [142] BMP-4/-6/-7 [125,126] VEGF [119,120] Epo [121] IGF-I [128,129] OGP [127] Leptin [130] PDGF [131] ephrinB2 [132] ITGA2 [133] NELL1 [134] β-catenin [135] HI Cb TA Fo Na LIVER REGENERATION VEGF [144] ATP7B [155] HN HN…”

Proliferation and osteogenic differentiation of rat BMSCs on a novel Ti/SiC metal matrix nanocomposite modified by friction stir processing

“…The expression levels of the angiogenesis-related markers VEGF, ANG-1 and HIF-1α were detected. It is well known that these angiogenic factors could simultaneously promote osteogenesis and angiogenesis8386. VEGF is a key angiogenic factor for enhancing blood vessel formation that effectively regulates biological activity87.…”

The Possible Roles of Biological Bone Constructed with Peripheral Blood Derived EPCs and BMSCs in Osteogenesis and Angiogenesis

“…Evidences reveal that VEGF, as a key angiogenic and paracrine angiogenic factor, has the ability to (i) simultaneously promote osteogenesis and angiogenesis [27, 28]; (ii) specifically target vascular endothelial cells and subsequently induced endothelial angiogenesis [29, 30]; (iii) increase the permeability of small veins and venules [31]. It is well known that ALP, Collagen Type I, and Osteonectin are the major biological markers in osteoblasts differentiation.…”