Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone development

Duan, Xuchen; Murata, Yurie; Li, Yanqiu; Nicolae, Claudia M.; Olsen, Bjørn R.; Berendsen, Agnes D.

doi:10.1242/dev.117952

Cited by 79 publications

(66 citation statements)

References 28 publications

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“…Interestingly, previous work has also identified a role for these signaling pathways, including their effectors such as ERK1/2, in driving endochondral ossification, either in the cranial base directly or other endochondral bones 60-65 . VEGFR1 (Flt1) and/or VEGFR2 (Flk1) are also excellent RTK candidates that might function in concert with MEMO1 as disruption to VEGF signaling results in reduced ossification associated with decreased vascularity and an elongated hypertrophic zone, similar to Memo1 mutants 66-68 . In addition, MEMO1 has been shown to interact with and influence downstream signaling from the estrogen receptor, another key pathway essential for bone development and homeostasis 59,69 .…”

Section: Discussionmentioning

confidence: 99%

MEMO1 drives cranial endochondral ossification and palatogenesis

Otterloo

Feng

Jones

et al. 2016

Developmental Biology

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The cranial base is a component of the neurocranium and has a central role in the structural integration of the face, brain and vertebral column. Consequently, alteration in the shape of the human cranial base has been intimately linked with primate evolution and defective development is associated with numerous human facial abnormalities. Here we describe a novel recessive mutant mouse strain that presented with a domed head and fully penetrant cleft secondary palate coupled with defects in the formation of the underlying cranial base. Mapping and non-complementation studies revealed a specific mutation in Memo1 - a gene originally associated with cell migration. Expression analysis of Memo1 identified robust expression in the perichondrium and periosteum of the developing cranial base, but only modest expression in the palatal shelves. Fittingly, although the palatal shelves failed to elevate in Memo1 mutants, expression changes were modest within the shelves themselves. In contrast, the cranial base, which forms via endochondral ossification had major reductions in the expression of genes responsible for bone formation, notably matrix metalloproteinases and markers of the osteoblast lineage, mirrored by an increase in markers of cartilage and extracellular matrix development. Concomitant with these changes, mutant cranial bases showed an increased zone of hypertrophic chondrocytes accompanied by a reduction in both vascular invasion and mineralization. Finally, neural crest cell-specific deletion of Memo1 caused a failure of anterior cranial base ossification indicating a cell autonomous role for MEMO1 in the development of these neural crest cell derived structures. However, palate formation was largely normal in these conditional mutants, suggesting a non-autonomous role for MEMO1 in palatal closure. Overall, these findings assign a new function to MEMO1 in driving endochondral ossification in the cranium, and also link abnormal development of the cranial base with more widespread effects on craniofacial shape relevant to human craniofacial dysmorphology.

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Section: Discussionmentioning

confidence: 99%

MEMO1 drives cranial endochondral ossification and palatogenesis

Otterloo

Feng

Jones

et al. 2016

Developmental Biology

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“…VEGFR2 (or KDR) is the main receptor for VEGFA, and signaling via this receptor triggers processes inducing cell migration, proliferation and survival in ECs (Olsson et al, 2006). VEGFR2 is also expressed by VEGF-producing cells of the osteoblast lineage and controls their migration, differentiation and survival in an autocrine fashion (Duan et al, 2015;Hu and Olsen, 2016) (Fig. 6).…”

Section: Vegf Signaling During Endochondral Angiogenesismentioning

confidence: 99%

Blood vessel formation and function in bone

2016

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In addition to their conventional role as a conduit system for gases, nutrients, waste products or cells, blood vessels in the skeletal system play active roles in controlling multiple aspects of bone formation and provide niches for hematopoietic stem cells that reside within the bone marrow. In addition, recent studies have highlighted roles for blood vessels during bone healing. Here, we provide an overview of the architecture of the bone vasculature and discuss how blood vessels form within bone, how their formation is modulated, and how they function during development and fracture repair.

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“…This suggests that paracrine activities of VEGF may include both expansion of endothelial cells and further stimulating them to generate growth factors for malignant cells. As other cell populations in the bone marrow microenvironment such as osteolineage cells also express VEGF receptors [127], it is possible that VEGF-mediated activity of other cell types may also contribute malignant clone proliferation. Therefore, the pro-survival and growth effects of VEGF may occur via both autocrine and paracrine signaling pathways to promote the proliferation and self-renewal of malignant clones, contributing to the progression of MDS and other hematologic malignancies.…”

Section: Vascular and Endothelial Alterations In Mds And Other Hematomentioning

confidence: 99%

The microenvironment in myelodysplastic syndromes: Niche-mediated disease initiation and progression

Calvi

2017

Experimental Hematology

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Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although identification of hematopoietic aberrations in human MDS has contributed significantly to our understanding of MDS pathogenesis, evidence now identify the bone marrow microenvironment (BMME) as another key contributor to disease initiation and progression. With improved understanding of the BMME, we are beginning to refine the role of the hematopoietic niche in MDS. Despite genetic diversity in MDS, interaction between MDS and the BMME appears to be a common disease feature, and therefore represents an appealing therapeutic target. Further understanding of the interdependent relationship between MDS and its niche is needed to delineate the mechanisms underlying hematopoietic failure and how the microenvironment can be clinically targeted. This review will provide an overview of data from human MDS and murine models supporting a role for BMME dysfunction at several steps of disease pathogenesis. While no models or human studies so far have combined all these findings, we will review current data identifying BMME involvement in each step of MDS pathogenesis, organized to reflect the chronology of BMME contribution as the normal hematopoietic system becomes myelodysplastic and MDS progresses to marrow failure and transformation. Although microenvironmental heterogeneity and dysfunction certainly add complexity to this syndrome, data are already demonstrating that targeting microenvironmental signals may represent novel therapeutic strategies for MDS treatment.

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Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone development

Cited by 79 publications

References 28 publications

MEMO1 drives cranial endochondral ossification and palatogenesis

MEMO1 drives cranial endochondral ossification and palatogenesis

Blood vessel formation and function in bone

The microenvironment in myelodysplastic syndromes: Niche-mediated disease initiation and progression

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