The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

John A Kessler - One of the best experts on this subject based on the ideXlab platform.

  • The dynamic role of Bone Morphogenetic Proteins in neural stem cell fate and maturation
    Developmental Neurobiology, 2012
    Co-Authors: Allison M. Bond, Oneil G. Bhalala, John A Kessler
    Abstract:

    The Bone Morphogenetic Proteins (BMPs) are a group of powerful morphogens that are critical for development of the nervous system. The effects of BMP signaling on neural stem cells are myriad and dynamic, changing with each stage of development. During early development inhibition of BMP signaling differentiates neuroectoderm from ectoderm, and BMP signaling helps to specify neural crest. Thus modulation of BMP signaling underlies formation of both the central and peripheral nervous systems. BMPs secreted from dorsal structures then form a gradient which helps pattern the dorsal-ventral axis of the developing spinal cord and brain. During forebrain development BMPs sequentially induce neurogenesis and then astrogliogenesis and participate in neurite outgrowth from immature neurons. BMP signaling also plays a critical role in maintaining adult neural stem cell niches in the subventricular zone (SVZ) and subgranular zone (SGZ). BMPs are able to exert such diverse effects through closely regulated temporospatial expression and interaction with other signaling pathways.

  • Bone Morphogenetic Proteins regulate enteric gliogenesis by modulating ErbB3 signaling.
    Developmental biology, 2010
    Co-Authors: Alcmène Chalazonitis, Fabien D'autréaux, Tuan D. Pham, Michael D. Gershon, John A Kessler
    Abstract:

    The neural crest-derived cell population that colonizes the bowel (ENCDC) contains proliferating neural/glial progenitors. We tested the hypothesis that Bone Morphogenetic Proteins (BMPs 2 and 4), which are known to promote enteric neuronal differentiation at the expense of proliferation, function similarly in gliogenesis. Enteric gliogenesis was analyzed in mice that overexpress the BMP antagonist, noggin, or BMP4 in the primordial ENS. Noggin-induced loss-of-function decreased, while BMP4-induced gain-of-function increased the glial density and glia/neuron ratio. When added to immunoisolated ENCDC, BMPs provoked nuclear translocation of phosphorylated SMAD Proteins and enhanced both glial differentiation and expression of the neuregulin receptor ErbB3. ErbB3 transcripts were detected in E12 rat gut, before glial markers are expressed; moreover, expression of the ErbB3 ligand, glial growth factor 2 (GGF2) escalated rapidly after its first detection at E14. ErbB3-immunoreactive cells were located in the ENS of fetal and adult mice. GGF2 stimulated gliogenesis and proliferation and inhibited glial cell derived neurotrophic factor (GDNF)-promoted neurogenesis. Enhanced glial apoptosis occurred following GGF2 withdrawal; BMPs intensified this GGF2-dependence and reduced GGF2-stimulated proliferation. These observations support the hypotheses that BMPs are required for enteric gliogenesis and act by promoting responsiveness of ENCDC to ErbB3 ligands such as GGF2.

  • Bone Morphogenetic Proteins induce apoptosis and growth factor dependence of cultured sympathoadrenal progenitor cells
    Developmental Biology, 1998
    Co-Authors: Qingbin Song, Mark F. Mehler, John A Kessler
    Abstract:

    Abstract Neuron numbers in developing vertebrate organisms are regulated by the availability of growth factors which promote their survival. However, neuron survival may also be regulated by growth factors which promote rather than prevent cell death. This study examined the effects of Bone Morphogenetic Proteins (BMPs) in inducing apoptosis of MAH cells, an immortalized sympathoadrenal progenitor cell line. Treatment of MAH cells with BMP2 or BMP4 killed the cells in a dose-dependent manner. By contrast, treatment with BMP7 or TGFβ1 failed to affect survival, suggesting that induction of apoptosis is specific to the dpp subgroup of BMPs. Survival after treatment with BMP2 or BMP4 required addition of fibroblast growth factor (FGF) and nerve growth factor (NGF), indicating that BMP treatment made the neurons dependent upon an exogenous factor for survival. Several experimental observations suggested an apoptotic mechanism for BMP-induced death. After BMP2 treatment, the cells progressively shrank and became pyknotic. Further, there was prominent endonucleosomic cleavage of DNA (laddering) as well as TUNEL staining. Moreover, BMP-induced death was inhibited by the caspase inhibitor z-VAD and was partially prevented by the endonuclease inhibitor aurintricarboxylic acid. These observations suggest that neuron numbers may be regulated by factors which promote death and that exposure to such factors may be a signal for the development of dependence upon other growth factors for survival.

  • Bone Morphogenetic Proteins in the nervous system
    Trends in Neurosciences, 1997
    Co-Authors: Mark F. Mehler, Peter C. Mabie, Damin Zhang, John A Kessler
    Abstract:

    Bone Morphogenetic Proteins (BMPs) are a rapidly expanding subclass of the transforming growth factor superfamily. BMP ligands and receptor subunits are present throughout neural development within discrete regions of the embryonic brain and within neural crest-derived pre- and postmigratory zones. BMPs initially inhibit the formation of neuroectoderm during gastrulation while, within the neural tube, they act as gradient morphogens to promote the differentiation of dorsal cell types and intermediate cell types throughout co-operative signaling. In the peripheral nervous system, BMPs act as instructive signals for neuronal lineage commitment and promote graded stages of neuronal differentiation. By contrast, within the CNS, these same factors promote astroglial lineage elaboration from embryonic subventricular zone progenitor cells, with concurrent suppression of the neuronal or oligodendroglial lineages, or both. In addition, BMPs act on more lineage- restricted embryonic CNS progenitor cells to promote regional neuronal survival and cellular differentiation. Furthermore, these versatile cytokines induce selective apoptosis of discrete rhombencephalic neural crest- associated cellular populations. These observations suggest that the BMPs exhibit a broad range of cellular and context-specific effects during multiple stages of neural development.

  • Bone Morphogenetic Proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells
    Neuron, 1996
    Co-Authors: Robert E Gross, Peter C. Mabie, Mark F. Mehler, Ziying Zang, Linda Santschi, John A Kessler
    Abstract:

    Abstract The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor β superfamily, the Bone Morphogenetic Proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic subventricular zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny.

Sabine Bailly - One of the best experts on this subject based on the ideXlab platform.

  • Bone Morphogenetic Proteins in vascular homeostasis and disease
    Cold Spring Harbor Perspectives in Biology, 2018
    Co-Authors: Mariejose Goumans, Sabine Bailly, An Zwijsen, Peter Ten Dijke
    Abstract:

    It is well established that control of vascular morphogenesis and homeostasis is regulated by vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), Delta-like 4 (Dll4), angiopoietin, and ephrin signaling. It has become clear that signaling by Bone Morphogenetic Proteins (BMPs), which have a long history of studies in Bone and early heart development, are also essential for regulating vascular function. Indeed, mutations that cause deregulated BMP signaling are linked to two human vascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. These observations are corroborated by data obtained with vascular cells in cell culture and in mouse models. BMPs are required for normal endothelial cell differentiation and for venous/arterial and lymphatic specification. In adult life, BMP signaling orchestrates neo-angiogenesis as well as vascular inflammation, remodeling, and calcification responses to shear and oxidative stress. This review emphasizes the pivotal role of BMPs in the vascular system, based on studies of mouse models and human vascular disorders.

  • emerging role of Bone Morphogenetic Proteins in angiogenesis
    Cytokine & Growth Factor Reviews, 2009
    Co-Authors: Laurent David, Jeanjacques Feige, Sabine Bailly
    Abstract:

    Bone Morphogenetic Proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor β (TGFβ) superfamily. Recent observations clearly emphasize the emerging role of BMPs in angiogenesis: (i) two genetic vascular diseases (hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH)) are caused by mutations in genes encoding components of the BMP signalling pathway (endoglin, ALK1 and BMPRII). (ii) BMP9 has been identified as the physiological ligand of the endothelial receptor ALK1 in association with BMPRII. This review will focus on the diverse functions of BMPs in angiogenesis. We will propose a model that distinguishes the BMP2, BMP7 and GDF5 subgroups from the BMP9 subgroup on the basis of their functional implication in the two phases of angiogenesis (activation and maturation).

Clemens W G M Lowik - One of the best experts on this subject based on the ideXlab platform.

  • Bone Morphogenetic Proteins stimulate angiogenesis through osteoblast derived vascular endothelial growth factor a
    Endocrinology, 2002
    Co-Authors: Martine Deckers, Rutger L Van Bezooijen, Geertje Van Der Horst, Jakomijn Hoogendam, Chris Van Der Bent, Socrates E Papapoulos, Clemens W G M Lowik
    Abstract:

    During Bone formation and fracture healing there is a cross-talk between endothelial cells and osteoblasts. We previously showed that vascular endothelial growth factor A (VEGF-A) might be an important factor in this cross-talk, as osteoblast-like cells produce this angiogenic factor in a differentiation-dependent manner. Moreover, exogenously added VEGF-A enhances osteoblast differentiation. In the present study we investigated, given the coupling between angiogenesis and Bone formation, whether Bone Morphogenetic Proteins (BMPs) stimulate osteoblastogenesis and angiogenesis through the production of VEGF-A. For this we used the murine preosteoblast-like cell line KS483, which forms mineralized nodules in vitro, and an angiogenesis assay comprising 17-d-old fetal mouse Bone explants that have the ability to form tube-like structures in vitro. Treatment of KS483 cells with BMP-2, -4, and -6 enhanced nodule formation, osteocalcin mRNA expression, and subsequent mineralization after 18 d of culture. This wa...

  • Bone Morphogenetic Proteins stimulate angiogenesis through osteoblast derived vascular endothelial growth factor a
    Endocrinology, 2002
    Co-Authors: Martine Deckers, Jakomijn Hoogendam, Socrates E Papapoulos, Rutger L Van Bezooijen, Geertje Van Der Horst, Chris Van Der Bent, Clemens W G M Lowik
    Abstract:

    During Bone formation and fracture healing there is a cross-talk between endothelial cells and osteoblasts. We previously showed that vascular endothelial growth factor A (VEGF-A) might be an important factor in this cross-talk, as osteoblast-like cells produce this angiogenic factor in a differentiation-dependent manner. Moreover, exogenously added VEGF-A enhances osteoblast differentiation. In the present study we investigated, given the coupling between angiogenesis and Bone formation, whether Bone Morphogenetic Proteins (BMPs) stimulate osteoblastogenesis and angiogenesis through the production of VEGF-A. For this we used the murine preosteoblast-like cell line KS483, which forms mineralized nodules in vitro, and an angiogenesis assay comprising 17-d-old fetal mouse Bone explants that have the ability to form tube-like structures in vitro. Treatment of KS483 cells with BMP-2, -4, and -6 enhanced nodule formation, osteocalcin mRNA expression, and subsequent mineralization after 18 d of culture. This was accompanied by a dose-dependent increase in VEGF-A protein levels throughout the culture period. BMP-induced osteoblast differentiation, however, was independent of VEGF-A, as blocking VEGF-A activity by a VEGF-A antibody or a VEGF receptor 2 tyrosine kinase inhibitor did not affect BMP-induced mineralization. To investigate whether BMPs stimulate angiogenesis through VEGF-A, BMPs were assayed for their angiogenic activity. Treatment of Bone explants with BMPs enhanced angiogenesis. This was inhibited by soluble BMP receptor 1A or noggin. In the presence of a VEGF-A antibody, both unstimulated and BMP-stimulated angiogenesis were arrested. Conditioned media of KS483 cells treated with BMPs also induced a strong angiogenic response, which was blocked by antimouse VEGF-A but not by noggin. These effects were specific for BMPs, as TGF beta inhibited osteoblast differentiation and angiogenesis while stimulating VEGF-A production. These findings indicate that BMPs stimulate angiogenesis through the production of VEGF-A by osteoblasts. In conclusion, VEGF-A produced by osteoblasts in response to BMPs is not involved in osteoblast differentiation, but couples angiogenesis to Bone formation.

Georges Bou-saab - One of the best experts on this subject based on the ideXlab platform.

  • Bone Morphogenetic Proteins in vascular calcification
    Circulation Research, 2005
    Co-Authors: Keith A. Hruska, Suresh Mathew, Georges Bou-saab
    Abstract:

    Vascular calcification is a common problem among the elderly and those with chronic kidney disease (CKD) and diabetes. The process of tunica media vascular calcification in CKD appears to involve a phenotypic change in the vascular smooth muscle cell (VSMC) resulting in cell-mediated mineralization of the extracellular matrix. The Bone Morphogenetic Proteins (BMPs) are important regulators in orthotopic Bone formation, and their localization at sites of vascular calcification raises the question of their role. In this review, we will discuss the actions of the BMPs in vascular calcification. Although the role of BMP-2 in vascular calcification is not proven, it has been the most studied member of the BMP family in this disease process. The role of BMP-2 may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2, or by inducing apoptosis of VSMCs, a process thought critical in the initiation of vascular calcification. Additionally, BMP-2 may be related to loss of regulation of the matrix Gla protein. A second BMP, BMP-7, less studied than BMP-2 may have opposing actions in vascular calcification. In postnatal life, BMP-7 is expressed primarily in the kidney, and expression is diminished by renal injury. BMP-7 is an important regulator of skeletal remodeling and the VSMC phenotype. BMP-7 restores skeletal anabolic balance in animal models of CKD with disordered skeletal modeling, also reducing serum phosphate in the process. BMP-7 also reverses vascular calcification in CKD, and reduction in vascular calcification is due, in part, to reduced serum phosphate, an important inducer of VSMC-mediated vascular mineralization and in part to direct actions on the VSMC.

Hari A Reddi - One of the best experts on this subject based on the ideXlab platform.

  • Bone Morphogenetic Proteins an unconventional approach to isolation of first mammalian morphogens
    Cytokine & Growth Factor Reviews, 1997
    Co-Authors: Hari A Reddi
    Abstract:

    Abstract It is conventional to identify morphogens from fly and frog embryos during morphogenesis using genescreens, substractive hybridizations, differential displays and expression cloning. This information is then extended to mice and men. The Bone Morphogenetic Proteins (BMPs) area family of pleiotropic morphogens/cytokines isolated and cloned from the demineralized extracellular matrix of adult Bone. Thus, BMPs were isolated from mammalian Bone by an unconventional approach. BMPs initiate the sequential developmental cascade of Bone morphogenesis in ectopic sites. The pleiotropic effects of BMPs on chemotaxis, mitosis and differentiation are based on concentration-dependent thresholds. Recent work has demonstrated the critical role of BMPs in pattern formation in amphibian and chick limb development. Targeted disruption of gene function by homologous recombination has demonstrated the actions of BMPs beyond Bone in such disparate tissues as kidney, eye, testis, teeth, skin and heart. The successful isolation of first mammalian morphogens has laid the foundation for the elucidation of molecular signalling during morphogenesis in Bones and beyond.

  • tissue engineering morphogenesis and regeneration of the periodontal tissues by Bone Morphogenetic Proteins
    Critical Reviews in Oral Biology & Medicine, 1997
    Co-Authors: Ugo Ripamonti, Hari A Reddi
    Abstract:

    Tissue engineering is the emerging field of science developing techniques for fabrication of new tissues for replacement based on principles of cell and developmental biology and biomaterials. Morphogenesis is the cascade of pattern formation and the attainment of form of the various organs and the organism as a whole. The periodontium consists of the periodontal ligament, cementum, and alveolar Bone. Bone has considerable potential for regeneration and therefore is a prototypic model for tissue engineering. The three main ingredients for tissue engineering are regulatory signals, responding stem cells, and extracellular matrix. Recent advances in molecular biology of the Bone Morphogenetic Proteins (BMPs) have set the stage for tissue engineering of Bone and related tissues, including the periodontium. Bone-derived BMPs, with a collagenous matrix as carrier, induced cementum and alveolar Bone regeneration in surgically created furcation defects in the primate. It is noteworthy that there was morphogenesi...

  • regulation of cartilage and Bone differentiation by Bone Morphogenetic Proteins
    Current Opinion in Cell Biology, 1992
    Co-Authors: Hari A Reddi
    Abstract:

    Quantum advances have recently been made in the understanding of the regulation of cartilage and Bone differentiation through the identification, purification, genetic cloning and expression of recombinant Bone Morphogenetic Proteins. Bone Morphogenetic Proteins are a family of pleiotropic differentiation factors with actions on chemotaxis, mitosis, initiation and promotion of chondrogenic and osteogenic phenotypes. They bind extracellular matrix components, heparin and type IV collagen and initiate Bone repair. The cascade of cartilage and Bone differentiation consists of several continuous phases: initiation, promotion, maintenance and termination.