VEGFR2 activation mediates the pro-angiogenic activity of BMP4

Rezzola, Sara; Somma, Margherita Di; Corsini, Michela; Leali, Daria; Ravelli, Cosetta; Polli, Viviane Aparecida Balvedi; Grillo, Elisabetta; Presta, Marco; Mitola, Stefania

doi:10.1007/s10456-019-09676-y

Cited by 39 publications

(26 citation statements)

References 56 publications

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“…Besides these, many tissue types exist in the bone, including vascular endothelium and connective tissues and autonomic and sensory nerves, which contribute to forming a favorable milieu for bone formation 48,49 . BMPs belong to the TGF-β super-family, which are recognized as playing critical roles in regulating bone formation and proliferation 50,51 , as well as in angiogenesis 52,53 . However, some members of BMPs can commit MSCs to osteoblast lineages, such BMP2, BMP4, BMP6, and BMP7 54,55 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

Liu

Tang

et al. 2020

Cell Death Dis

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Human amniotic mesenchymal stem cells (hAMSCs) are multiple potent progenitor cells (MPCs) that can differentiate into different lineages (osteogenic, chondrogenic, and adipogenic cells) and have a favorable capacity for angiogenesis. Schnurri-3 (Shn3) is a large zinc finger protein related to Drosophila Shn, which is a critical mediator of postnatal bone formation. Bone morphogenetic protein 9 (BMP9), one of the most potent osteogenic BMPs, can strongly upregulate various osteogenesis-and angiogenesis-related factors in MSCs. It remains unclear how Shn3 is involved in BMP9-induced osteogenic differentiation coupled with angiogenesis in hAMSCs. In this investigation, we conducted a comprehensive study to identify the effect of Shn3 on BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs and analyze the responsible signaling pathway. The results from in vitro and in vivo experimentation show that Shn3 notably inhibits BMP9-induced early and late osteogenic differentiation of hAMSCs, expression of osteogenesis-related factors, and subcutaneous ectopic bone formation from hAMSCs in nude mice. Shn3 also inhibited BMP9-induced angiogenic differentiation, expression of angiogenesis-related factors, and subcutaneous vascular invasion in mice. Mechanistically, we found that Shn3 prominently inhibited the expression of BMP9 and activation of the BMP/Smad and BMP/MAPK signaling pathways. In addition, we further found activity on runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF), and the target genes shared by BMP and Shn3 signaling pathways. Silencing Shn3 could dramatically enhance the expression of Runx2, which directly regulates the downstream target VEGF to couple osteogenic differentiation with angiogenesis. To summarize, our findings suggested that Shn3 significantly inhibited the BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs. The effect of Shn3 was primarily seen through inhibition of the BMP/Smad signaling pathway and depressed expression of Runx2, which directly regulates VEGF, which couples BMP9-induced osteogenic differentiation with angiogenesis.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

Liu

Tang

et al. 2020

Cell Death Dis

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“…20 A cascade involving exogenously applied bone morphogenetic protein (BMP)-4, proto-oncogene c-Src and the VEGFR-2 has been found to promote angiogenesis. 21 The chick skeleton develops from calcium mobilised predominantly from the eggshell, transported via a calcium binding protein (CBP) in the ectoderm of the CAM, which is closely associated with a Ca 2+ -ATPase, with 85%-95% of calcium previously provided by the yolk sac during the first 10 days. [22][23][24][25][26][27] The calcium from the shell is mobilised via the enzyme carbonic anhydrase, at EDs 11 to 12, until hatching occurs at ED 21.…”

Section: The Cammentioning

confidence: 99%

“… 20 A cascade involving exogenously applied bone morphogenetic protein (BMP)-4, proto-oncogene c-Src and the VEGFR-2 has been found to promote angiogenesis. 21 …”

Section: The Cammentioning

confidence: 99%

“…The main use in research of the CAM is in the assessment of angiogenic, 21 , 41 anti-angiogenic or toxic 42 responses to drugs, 43 cells, extracellular vesicles 44 or materials, 3 biocompatibility of materials, 45 the growth or treatment of cancer 46 – 48 and xenograft application 49 – 52 for tissue growth and testing treatment modalities. Oncology research remains, to date, the most common field using the CAM assay.…”

Section: Current Common Applications Of the Cam In Researchmentioning

confidence: 99%

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Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

2020

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The chick chorioallantoic membrane model has been around for over a century, applied in angiogenic, oncology, dental and xenograft research. Despite its often perceived archaic, redolent history, the chorioallantoic membrane assay offers new and exciting opportunities for material and growth factor evaluation in bone tissue engineering. Currently, superior/improved experimental methodology for the chorioallantoic membrane assay are difficult to identify, given an absence of scientific consensus in defining experimental approaches, including timing of inoculation with materials and the analysis of results. In addition, critically, regulatory and welfare issues impact upon experimental designs. Given such disparate points, this review details recent research using the ex vivo chorioallantoic membrane assay and the ex vivo organotypic culture to advance the field of bone tissue engineering, and highlights potential areas of improvement for their application based on recent developments within our group and the tissue engineering field.

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“…The collagen gel invasion assay was performed on HUVEC spheroids [23]. Briefly, spheroids were prepared in 20% methylcellulose medium, embedded in collagen gel or collagen gel:Histogel (1:5) in the absence or in the presence of ADSCs or differentiated cells.…”

Section: Methodsmentioning

confidence: 99%

Natural Histogel-Based Bio-Scaffolds for Sustaining Angiogenesis in Beige Adipose Tissue

Somma

Schaafsma²,

Grillo

et al. 2019

Cells

Self Cite

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In the treatment of obesity and its related disorders, one of the measures adopted is weight reduction by controlling nutrition and increasing physical activity. A valid alternative to restore the physiological function of the human body could be the increase of energy consumption by inducing the browning of adipose tissue. To this purpose, we tested the ability of Histogel, a natural mixture of glycosaminoglycans isolated from animal Wharton jelly, to sustain the differentiation of adipose derived mesenchymal cells (ADSCs) into brown-like cells expressing UCP-1. Differentiated cells show a higher energy metabolism compared to undifferentiated mesenchymal cells. Furthermore, Histogel acts as a pro-angiogenic matrix, induces endothelial cell proliferation and sprouting in a three-dimensional gel in vitro, and stimulates neovascularization when applied in vivo on top of the chicken embryo chorioallantoic membrane or injected subcutaneously in mice. In addition to the pro-angiogenic activity of Histogel, also the ADSC derived beige cells contribute to activating endothelial cells. These data led us to propose Histogel as a promising scaffold for the modulation of the thermogenic behavior of adipose tissue. Indeed, Histogel simultaneously supports the acquisition of brown tissue markers and activates the vasculature process necessary for the correct function of the thermogenic tissue. Thus, Histogel represents a valid candidate for the development of bioscaffolds to increase the amount of brown adipose tissue in patients with metabolic disorders.

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VEGFR2 activation mediates the pro-angiogenic activity of BMP4

Cited by 39 publications

References 56 publications

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

Natural Histogel-Based Bio-Scaffolds for Sustaining Angiogenesis in Beige Adipose Tissue

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