Roles of exogenously regulated bFGF expression in angiogenesis and bone regeneration in rat calvarial defects

Abstract

Abstract. Regulation of transgene expression and function is important for gene therapy because it allows complex biological processes to be controlled and monitored. Basic fibroblast growth factor (bFGF) is an effective angiogenic factor and bone regeneration factor; it can induce differentiation of mesenchymal stem cells (MSCs) in vitro and bone regeneration in vivo. Further, exogenous regulation of controllable bFGF expression in the bone regeneration area safely allows bone formation and regeneration. In our study, we constructed a recombinant adeno-associated virus type 2 (rAAV2)-based bFGF gene delivery system, which is regulated by tetracycline or doxycycline (Dox, an analogue of tetracycline). We evaluated the regulatory effects of this system on bFGF transgenic expression in vitro and in vivo. We found that bFGF could increase the mRNA expression levels of osteoblast differentiation factor and the activity of alkaline phosphatase (ALP). Dox could effectively regulate bFGF expression, thus controlling MSC differentiation. After in vivo transplantation of genetically engineered MSCs, animals not treated with Dox showed significant bone formation and angiogenesis compared with the group treated with dox. dox may also effectively regulate angiogenesis and bone regeneration in vivo. Therefore, the inducible bFGF system is an effective way of regulating bone regeneration and formation.

Basic fibroblast growth factor regulates phosphate/pyrophosphate regulatory genes in stem cells isolated from human exfoliated deciduous teeth

“…The anabolic effect of bFGF in vivo could result from the brief exposure of local cells to the released proteins, prompting osteogenic differentiation. In addition, bFGF regulates angiogenesis, cell migration, and cell proliferation [ 71 , 72 ]. Hence, these processes could help to facilitate the healing and formation of hard tissue in vivo .…”

The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells

“…However, previous research has mostly focused on the secretion of angiogenic factors by undifferentiated bone marrow derived MSCs such as mesenchymal progenitor cells, marrow-derived stromal cells and multipotent stromal cells [ 79 – 81 ]; moreover, recent studies reported that the osteogenically differentiated MSCs that cultured in osteogenic induction medium could lead cells antiangiogenic and reduce the secretion of angiogenic factors like VEGF and platelet-derived growth factor-AA (PDGF-AA) [ 82 , 83 ]. However, many studies reported that some growth factors such as BMP-2 [ 84 , 85 ], BMP-9 [ 86 ], epidermal growth factor (EGF) [ 87 ], growth and differentiation factor-5 (GDF-5) [ 88 ] and basic fibroblast growth factor (bFGF) [ 84 , 89 , 90 ], could promote osteogenic differentiation of MSCs as well as secretion of angiogenic factors by inducing both osteogenic and angiogenic signaling pathways without osteogenic induction medium. In the present study, it has been firstly observed that as a kind of Chinese medicine, quercetin could not only promote osteogenic differentiation of rBMSCs, but also enhance the secretion of angiogenic factors in a dose-dependent manner, while the concentration of 2 μM could achieve the greatest effect.…”

Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs

“…Among the known BMPs, BMP-2 has the most pronounced effect on promoting defect repair and in healing fractures [33]. bFGF, a potent angiogenic factor and bone regeneration factor, induces specialization of MSCs in vitro and bone repair in vivo [17]. bFGF-modified BMSCs could accelerate healing after anterior cruciate ligament (ACL) reconstruction.…”

“…BMP-2, one of the most effective osteoinductive proteins, facilitates osteoblast differentiation, and prior studies have demonstrated that bone repair can be accomplished through the application of BMP-2 [14, 16]. Basic fibroblast growth factor (bFGF) has important roles in a wide variety of cellular functions, including cell multiplication and angiogenesis [17], and due to its effects on gene expression and angiogenesis, it is a key factor during bone repair [18]. Adenovirus vectors have proven to be potent gene delivery vehicles that can be used to genetically manipulate cells [19].…”