Sclerostin is a potent inhibitor of Wnt signaling and bone formation. However, there is currently no information on the relation of circulating sclerostin levels to age, gender, or bone mass in humans. Thus we measured serum sclerostin levels in a population-based sample of 362 women [123 premenopausal, 152 postmenopausal not on estrogen treatment (ET), and 87 postmenopausal on ET] and 318 men, aged 21 to 97 years. Sclerostin levels (mean ± SEM) were significantly higher in men than women (33.3 ± 1.0 pmol/L versus 23.7 ± 0.6 pmol/L, p , .001). In pre- and postmenopausal women not on ET combined (n = 275) as well as in men, sclerostin levels were positively associated with age (r = 0.52 and r = 0.64, respectively, p , .001 for both). Over life, serum sclerostin levels increased by 2.4- and 4.6-fold in the women and men, respectively. Moreover, for a given total-body bone mineral content, elderly subjects (age ≥ 60 years) had higher serum sclerostin levels than younger subjects (ages 20 to 39 ...

Bone morphogenetic protein 5 is a protein that in humans is encoded by the BMP5 gene. The protein encoded by this gene is member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce bone and cartilage development. BMP5 may play a role in certain cancers. Like other BMPs BMP5 is inhibited by chordin and noggin. It is expressed in the trabecular meshwork and optic nerve head and may have a role in the development and normal function. It is also expressed in the lung and liver. This gene encodes a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. These proteins are synthesized as prepropeptides, cleaved, and then processed into dimeric proteins. This ...

Bone morphogenetic protein 5 is a protein that in humans is encoded by the BMP5 gene.[1][2][3] The protein encoded by this gene is member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce bone and cartilage development. BMP5 may play a role in certain cancers. Like other BMPs BMP5 is inhibited by chordin and noggin. It is expressed in the trabecular meshwork and optic nerve head and may have a role in the development and normal function. It is also expressed in the lung and liver. This gene encodes a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. These proteins are synthesized as prepropeptides, cleaved, and then processed into dimeric ...

Bone morphogenetic protein 3, also known as osteogenin, is a protein in humans that is encoded by the BMP3 gene. The protein encoded by this gene is a member of the transforming growth factor beta superfamily. It, like other bone morphogenetic proteins (BMPs) is known for its ability to induce bone and cartilage development. It is a disulfide-linked homodimer. It negatively regulates bone density. BMP3 is an antagonist to other BMPs in the differentiation of osteogenic progenitors. It is highly expressed in fractured tissues. GRCh38: Ensembl release 89: ENSG00000152785 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000029335 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: BMP3 bone morphogenetic protein 3 (osteogenic). Human BMP3 genome location and BMP3 gene details page in the UCSC Genome Browser. Dickinson ME, Kobrin MS, Silan CM, Kingsley DM, Justice MJ, Miller DA, Ceci JD, Lock LF, Lee A, Buchberg AM (March 1990). Chromosomal ...

The molecular factors that regulate cardiac differentiation have been extensively studied, yet, relatively little is known about how cardiomyocytes acquire atrial versus ventricular characteristics. Embryonic stem (ES) cells, which have the potential to differentiate to a wide array of distinct cell types, including most types of cardiovascular cells, offer a pertinent in vitro model to work out the molecular mechanisms of atrial specification and differentiation. We discovered that the secreted antagonist of BMP signaling, Protein Related to Dan and Cerberus (PRDC, also called Gremlin2) leads to a surge in cardiomyocytic differentiation when applied to mouse ES-derived cardiac progenitor cells. This property is unique to PRDC among tested BMP antagonists. Lineage expansion is restricted to cardiomyocytes, with the differentiation of endodermal, blood, endothelial and neuronal cells being unaffected. Using molecular and electrophysiological analyses, we show that PRDC-induced cardiomyocytes ...

|p|Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins. BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is involved also in cardiac cell differentiation and epithelial to mesenchymal transition. BMP-2 and BMP-7 are osteogenic BMPs: they have been demonstrated to potently induce osteoblast differentiation in a variety of cell types.|/p||p|Bone morphogenetic protein 2 is shown to stimulate the production of bone and recombinant human protein (rhBMP-2) and is currently available for orthopaedic usage in the United States.|/p|

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Objective: Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice. Approach and Results MGP-deficient mice (MGP-/-) were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP-/- mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P,0.001 for both). LDN-193189-treated MGP-/- mice survived ...

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The importance of morphogenetic proteins (BMPs) and their antagonists in vascular development is increasingly being recognized. BMP-4 is essential for angiogenesis and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both induced in a staged fashion by the activin-like kinase receptor 1 (ALK1) after stimulation by BMP-9. In this study, however, we show that CV2 preferentially binds and inhibits BMP-9 thereby providing strong feedback inhibition for BMP-9/ALK1 signaling rather than for BMP-4/ALK2 signaling. CV2 disrupts complex formation by ALK2, ALK1, BMP-4 and BMP-9 required for the induction of both BMP antagonists. It also limits VEGF expression and proliferation of ALK1-expressing endothelial cells. In vivo, CV2 deficiency translates into a dysregulation of vascular BMP signaling, resulting in a thickened, abnormal endothelium with increased markers of endothelial differentiation. Thus, mutual regulation by BMP-9 and CV2 is essential in regulating the development of the ...

Buy anti-BMP7 antibody, Mouse anti-Human Bone Morphogenetic Protein 7 (BMP7) Monoclonal Antibody-NP_001710.1 (MBS2090573) product datasheet at MyBioSource, Primary Antibodies. Application: Western Blot (WB), Immunohistochemistry (IHC), Immunocytochemistry (ICC), Immunoprecipitation (IP)

Aim: Effective treatment of premature infants with bronchopulmonary dysplasia (BPD) is lacking. We hypothesize that bone morphogenetic protein 9 (BMP9), a ligand of the TGF-β family that binds to the activin receptor-like kinase 1 (ALK1)-BMP receptor type 2 (BMPR2) receptor complex, may be a novel therapeutic option for BPD. Therefore, we investigated the cardiopulmonary effects of BMP9 in neonatal Wistar rats with hyperoxia-induced BPD. Methods: Directly after birth Wistar rat pups were exposed to 100% oxygen for 10 days. From day 2 rat pups received BMP9 (2.5 µg/kg, twice a day) or 0.9% NaCl by subcutaneous injection. Beneficial effects of BMP9 on aberrant alveolar development, lung inflammation and fibrosis, and right ventricular hypertrophy (RVH) were investigated by morphometric analysis and cytokine production. In addition, differential mRNA expression of BMP9 and its receptor complex: ALK1, BMPR2 and Endoglin, and of the ALK1 downstream target transmembrane protein 100 (TMEM100) were studied

The bone morphogenetic protein (BMP) signaling cascade is aberrantly activated in human non-small cell lung cancer (NSCLC) but not in normal lung epithelial cells, suggesting that obstructing BMP signaling may be an effective therapeutic approach for lung cancer. cascades would become ideal for anticancer drug development. In a zebrafish embryo-based structure and activity study, we previously recognized a group of highly selective small molecule inhibitors specifically antagonizing the intracellular kinase website of BMP type I receptors. In the present study, we shown that DMH1, one of such inhibitors, potently reduced lung cell expansion, advertised cell death, and decreased cell migration and attack in NSCLC cells by obstructing BMP signaling, as indicated PD318088 by suppression of Smad 1/5/8 phosphorylation and gene appearance of Identification1, Id2 and Id3. Additionally, DMH1 treatment significantly PD318088 reduced the tumor growth in human being lung malignancy xenograft model. In ...

J:133691 Choi M, Stottmann RW, Yang YP, Meyers EN, Klingensmith J, The bone morphogenetic protein antagonist noggin regulates mammalian cardiac morphogenesis. Circ Res. 2007 Feb 2;100(2):220-8 ...

OBJECTIVE: To characterize the bone morphogenetic protein (BMP) target cells positive for phosphorylated (P-)SMAD1/5, in rheumatoid arthritis (RA) synovium. METHODS: Synovial biopsies were obtained by needle arthroscopy. Anti-P-SMAD1/5 antibodies were used for Western blot (WB) on protein extracts from RA and normal synovium and for immunostaining of synovial biopsy sections. Positive cells were further identified by double staining for CD3, CD20, CD68, CD138, CD90, alpha smooth muscle actin (SMA), endoglin (CD105) and von Willebrand factor (VWF). In sections from early RA patients taken before and under antirheumatic treatment, the degree of inflammation and activation of the BMP pathway were quantified. RESULTS: P-SMAD1/5 protein was detected by WB in RA and to a lesser extent in normal synovium. Different P-SMAD1/5 positive cell populations were identified in RA synovium, mainly in perivascular and sublining cells. P-SMAD1/5 positive perivascular cells were alpha SMA positive and located ...

Bone morphogenetic proteins (BMPs) are importantsignalling molecules that were first identified by their ability to induce bone and cartilage, and subsequently were shown to be pleiotropic cytokines controlling a wide variety of biological responses during early development, skeletogenesis and homoeostasis of several tissues

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A truncated bone morphogenetic protein 4 receptor alters the fate of ventral mesoderm to dorsal mesoderm: roles of animal pole tissue in the development of vent

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Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis: Bone morphogenetic pr

Bone morphogenetic protein signalling dynamics in hFOBs under two-dimensional and three-dimensional culture conditions. (a) hFOBs in two-dimensional monolayer c

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Bone Morphogenetic Proteins (BMPs), their structure, action and detailed description of BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7.

Noggin protein is a potent bone morphogenetic protein (BMP) antagonist capable of inhibiting vasculogenesis even in the presence of provasculogenic VEGF and FGF-2. We found that human umbilical vein endothelial cells (HUVECs) do not express Noggin in culture and used these cells for modeling of antivasculogenesis. We hypothesized that high-efficiency transduction of HUVECs with bicistronic lentiviral vector encoding Noggin and enhanced green fluorescent protein (EGFP) enables direct visualization of Noggin effects in homogenous primary cell populations in vitro and in vivo. By comparing HUVECs transduced with a control GFP and GFP/Noggin expression cassettes, we showed that constitutive and orthotopic Noggin protein expression did not influence cell proliferation, down-regulated BMP-2 expression, and showed no effect on BMP receptor transcripts. We demonstrated that in contrast to GFP-only control, Noggin expression in endothelial cells abrogated endothelial migration in response to monolayer injury,

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Sclerostin inhibits unstimulated and BMP-stimulated osteoblastic differentiation of KS483 and primary human MSCs, but not of C2C12 cells. Silver staining (lanes 1 and 2) and Western blotting with a rabbit anti-human sclerostin antibody (lanes 3-8) of human sclerostin (lanes 2 [100 ng/ml], 3 [500 ng/ml], 5 [100 ng/ml], and 7 [100 ng/ml]), sclerostin containing medium of KS483 (lane 4), CHO cells (lane 6), and immunodepleted sclerostin preparation (lane 8, equal volume as 100 ng/ml sclerostin preparation) run under reducing conditions (A). Long-term (18 d) osteogenic KS483 cell cultures were treated with sclerostin (2.5 μg/ml or concentrations indicated) or CoM (equal volume) from day 4 onwards and analyzed for ALP activity (B) and mineralization (C). Confluent KS483 were stimulated with BMPs (50 ng/ml BMP-2, 50 ng/ml BMP-4, 300 ng/ml BMP-5, 100 ng/ml BMP-6, and 300 ng/ml BMP-7) in the absence or presence of the dose range of sclerostin or CoM. ALP activity was measured kinetically 4 d after ...

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016 ...

The present invention provides pharmaceutical compositions comprising a morphogenic protein stimulatory factor (MPSF) for improving the tissue inductive activity of morphogenic proteins, particularly

Using a biochemical approach, we confirmed the C-terminal region of HOXA13 folds into a functional DNA-binding motif and binds DNA in a sequence-specific manner. In vitro, the A13-DBD peptide facilitated the identification of HOXA13-binding sites upstream of Bmp2 and Bmp7. Quantitation of A13-DBD affinity for these enhancer elements revealed a novel series of nucleotide sequences that are preferentially bound with affinities almost 2-fold greater than the DNA regions bound by other homeodomain peptides (Catron et al., 1993).. In vivo, the interactions between HOXA13 and the Bmp2 and Bmp7 enhancer regions are conserved, as both enhancer elements were present in immunoprecipitated complexes of HOXA13 bound to DNA. The association of HOXA13 with the Bmp2 and Bmp7 enhancer regions in the developing limb strongly suggests that HOXA13 directly regulates the expression of these genes during autopod formation. It is important to note that because chromatin immunoprecipitations do not separate protein ...

Research proven goat polyclonal BMP-4 antibody. Initiates, promotes and regulates bone development, growth, remodeling and repair. Smad1 translocation to the nucleus is observed after the addition of BMP4. Designed for immunohistochemistry, western blotting and related applications.

Noggin is a secreted peptide that binds and inactivates Bone Morphogenetic Proteins, members of the transforming growth factor beta superfamily of secreted signaling molecules. In vertebrate limbs, Noggin is expressed in condensing cartilage and immature chondrocytes. Inactivation of the Noggin gene …

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Bone Morphogenetic Proteins (BMPs) are key regulators for a lot of diverse cellular processes. During embryonic development these proteins act as morphogens and play a crucial role particularly in organogenesis. BMPs have a direct impact on distinct cellular fates by means of concentration-gradients in the developing embryos. Using the diverse signaling input information within the embryo due to the gradient, the cells transduce the varying extracellular information into distinct gene expression profiles and cell fate decisions. Furthermore, BMP proteins bear important functions in adult organisms like tissue homeostasis or regeneration. In contrast to TGF-ß signaling, currently only little is known about how cells decode and quantify incoming BMP signals. There is poor knowledge about the quantitative relationships between signal input, transducing molecules, their states and location, and finally their ability to incorporate graded systemic inputs and produce qualitative responses. A key ...

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Although the efficacy of BMPs as stimulators of bone repair has been demonstrated in model systems and clinical studies, the use of BMPs to enhance fracture healing in the clinical setting is still controversial. Issues such as when, where and how much of which BMP is the most effective and profitab …

Gremlin-1 (isoform-1) belongs to a group of diffusible proteins which bind to ligands of the TGF- β family and regulate their activity by inhibiting their access to signaling receptors. The interplay between TGF-β ligands and their natural antagonists has major biological significance during development processes, in which cellular response can vary considerably depending upon the local concentration of the signaling molecule. Gremlin is highly expressed in the small intestine, fetal brain, and colon and lower expression in brain, prostate, pancreas and skeletal muscle. Gremlin-1 regulates multiple functions in early development by specifically binding to and inhibiting the function of BMP-2, -4, and -7. It also plays a role in carcinogenesis and kidney branching morphogenesis. Recombinant Gremlin-1 is a 18.4 kDa protein containing 161 amino acid residues ...

BMP compositions including the human factor and bovine factor thereof, the process of isolating BMP compositions and factors, and the use of such factors and compositions to induce bone formation in animals.

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In the present study, we explored the correlations of the BMP4 gene polymorphisms and the serum BMP4 levels with the development of LVH among Chinese EH patients. We found that the 6007C , T polymorphism of the BMP4 gene and the serum BMP4 level were significantly associated with the risk to develop LVH. Our in vitro study shows that the BMP4 inhibition in cardiomyocyte by si-RNA technique significantly decreased the Ang II induced cardiomyocyte size and protein content per cell, indicating the importance of BMP4 in the cardiomyocyte hypertrophy. Collectively, our data suggest that both the 6007C , T of the BMP4 gene and the serum BMP4 level may be used as potential marker for LVH incidence among the EH patients.. Bone morphogenetic proteins are osteoinductive growth factors that play a key role in cell differentiation, proliferation, migration, development, and apoptosis. BMP4 has been linked to the receptor-activator of nuclear factor-κB ligand (RANKL) mediated calcification in vessel smooth ...

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Human BMP2 ELISA Kit is a sensitive (| 2 pg/ml) immunoassay suitable for the quantification of BMP2 in Cell culture supernatant, Serum, Plasma, Other biological fluids, Tissue Extracts samples.

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Complete information for BMP8B gene (Protein Coding), Bone Morphogenetic Protein 8b, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Looking for online definition of bone morphogenetic protein 2B in the Medical Dictionary? bone morphogenetic protein 2B explanation free. What is bone morphogenetic protein 2B? Meaning of bone morphogenetic protein 2B medical term. What does bone morphogenetic protein 2B mean?

DOI: 10.11607/jomi.3543 To successfully rehabilitate edentulous patients using endosseous implants, there must be enough available bone. Several techniques have been proposed for augmentation of sites with insufficient bone volume. Although autogenous bone has long been considered the gold standard for such procedures, the limited availability of graft material and a high morbidity rate are potential disadvantages of this type of graft. An alternative is to use recombinant human bone morphogenetic protein 2 (rhBMP-2), which is able to support bone regeneration in the oral environment. These cases demonstrate the applicability of rhBMP-2 in maxillary sinus elevation and augmentation procedures in the maxilla to enable dental implant placement. The use of rhBMP-2 in alveolar augmentation procedures had several clinical benefits for these patients ...

Author(s): Heilmeier, U; Carpenter, DR; Patsch, JM; Harnish, R; Joseph, GB; Burghardt, AJ; Baum, T; Schwartz, AV; Lang, TF; Link, TM | Abstract: © 2015, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future. Introduction: Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture

Sclerostin, the product of the SOST gene, located on chromosome 17, locus q11.2 in humans, was originally believed to be a non-classical Bone morphogenetic protein (BMP) antagonist.More recently Sclerostin has been identified as binding to LRP5/6 receptors and inhibiting the Wnt signalling pathway .Wnt activation under these circumstances is antagonistic to bone formation. Although the underlying mechanisms are unclear, it is believed that the antagonism of BMP-induced bone formation by sclerostin is mediated by Wnt signalling, but not BMP signalling pathways.. Sclerostin is produced by the osteocyte and has catabolic effects on bone formation. This protein, with a length of 113 residues, has a dssp secondary structure that is 28% beta sheet (6 strands; 32 residues. Sclerostin has an inhibitory effect on the lifetime of the osteoblast. Sclerostin production by osteocytes is inhibited by parathyroid hormone, mechanical loading and cytokines including oncostatin M, cardiotrophin-1 and leukemia ...

Sclerostin, the product of the SOST gene, located on chromosome 17, locus q11.2 in humans, was originally believed to be a non-classical Bone morphogenetic protein (BMP) antagonist.More recently Sclerostin has been identified as binding to LRP5/6 receptors and inhibiting the Wnt signalling pathway .Wnt activation under these circumstances is antagonistic to bone formation. Although the underlying mechanisms are unclear, it is believed that the antagonism of BMP-induced bone formation by sclerostin is mediated by Wnt signalling, but not BMP signalling pathways.. Sclerostin is produced by the osteocyte and has catabolic effects on bone formation. This protein, with a length of 113 residues, has a dssp secondary structure that is 28% beta sheet (6 strands; 32 residues. Sclerostin has an inhibitory effect on the lifetime of the osteoblast. Sclerostin production by osteocytes is inhibited by parathyroid hormone, mechanical loading and cytokines including oncostatin M, cardiotrophin-1 and leukemia ...

BACKGROUND CONTEXT Increasingly, reports of frequent and occasionally catastrophic complications associated with use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal fusion surgeries are being published. In the original peer review, industry-sponsored publications describing the use of rhBMP-2 in spinal fusion, adverse events of these types and frequency were either not reported at all or not reported to be associated with rhBMP-2 use. Some authors and investigators have suggested that these discrepancies were related to inadequate peer review and editorial oversight. PURPOSE To compare the conclusions regarding the safety and related efficacy published in the original rhBMP-2 industry-sponsored trials with subsequently available Food and Drug Administration (FDA) data summaries, follow-up publications, and administrative and organizational databases. STUDY DESIGN Systematic review. METHODS Results and conclusions from original industry-sponsored rhBMP-2 publications regarding

Our data revealed that deficiency in CIZ increased basal bone mass in adult mice. This phenotype was through the enhancement of bone formation in vivo, increased mineralized nodule formation in bone marrow cells, and elevated expression levels of the genes encoding osteoblastic phenotype-related marker proteins including COL1, ALP, OPN, and OSX in bone in vivo. CIZ deficiency also enhanced bone marrow ablation-induced new bone formation in vivo as well as BMP injection-induced de novo osteogenesis in adult mice. Thus, CIZ acts as an inhibitor of bone formation in adult mice in vivo at least in part through its suppression of BMP actions.. CIZ localizes at adhesion plaques, transfers into nuclear compartments, binds to consensus DNA sequences, and activates promoters of the genes encoding enzymes that degrade matrix proteins (15). As CIZ is expressed in cultured osteoblasts (17-19), this protein was thought to be a modulator of osteoblastic function. However, there was an ambiguity regarding CIZ ...

Enhanced osteoinductivity of recombinant human bone morphogenetic protein-2 in combination with epidermal growth factor in a rabbit tibial defect model ...

BMP-14 is expressed in long bones during embryonic development and postnatally in articular cartilage. Mutations in the BMP-14 gene have been implicated in Grebe Syndrome, which is characterized by short stature, extra digits, short and deformed extremities, and in Hunter- Thompson type dwarfism. The mature and functional form of BMP-14 is a homodimer of two 120 amino-acid polypeptide chain (monomers) linked by a single disulfide bond. Each BMP-14 monomer is expressed as the C-terminal part of a precursor polypeptide, which also contains a 27 amino-acid signal peptide and a 354 amino-acid propeptide. This precursor undergoes intracellular dimerization, and upon secretion it is processed by a furin-type protease. Recombinant human BMP-14 is a 27.0 kDa homodimeric disulfide-linked protein consisting of two 120 amino acids ...

Our results identify BMPR2/ALK2 and BMPR2/ALK3 as key receptors that mediate proangiogenic BMP signaling in the early postnatal retina and reveal regional differences among BMPR1s by analysis of parallel genetic experiments in a defined vascular bed. Deletion of the common BMPR2 receptor reduced vascular sprouting and density. Deletion of ALK3, which is ubiquitously expressed in retinal endothelial cells, also dramatically reduced vascular sprouting and density, while loss of ALK2, which is enriched behind the vascular front, did not significantly affect sprouting but reduced overall vessel density. Therefore, we propose that spatially regulated BMPR1 expression fine-tunes endothelial cell responses to proangiogenic BMP ligands in development. Since expression of BMP ligands selective for ALK2 and ALK3 is elevated during retinal angiogenesis, it is tempting to speculate that BMP6/7-ALK2/3-BMPR2 signaling axis may provide essential input for the developing retina.. Since the phenotype of ...

Reliable and effective communication between neurons and their postsynaptic targets across the synaptic cleft is critical for the formation, growth, and plasticity of neuronal synapses. One mode of this transsynaptic communication is retrograde signaling, in which target cells provide molecular signals to influence presynaptic neurons (Tao and Poo, 2001; Marqués and Zhang, 2006). In Drosophila melanogaster, Glass bottom boat (Gbb), a bone morphogenetic protein (BMP), acts as a critical retrograde signal that promotes synaptic growth and neurotransmitter release at the neuromuscular junction (NMJ; Haghighi et al., 2003; McCabe et al., 2003; Goold and Davis, 2007). Genetic experiments have shown that the retrograde Gbb signal is sensed by a presynaptic receptor complex formed by the type II BMP receptor wishful thinking (Wit) and either of two type I BMP receptors, thick veins (Tkv) and saxophone (Sax; Aberle et al., 2002; Marqués et al., 2002; Rawson et al., 2003; McCabe et al., 2004; ...

The transforming growth factor β (TGF-β) superfamily comprises more than 30 ligands that play essential roles during early vertebrate development in the specification and subsequent patterning of the germ layers and in tissue homeostasis in adult organisms. Deregulation of signaling downstream of many of these ligands has been implicated in human diseases such as cancer and fibrosis, in wound healing disorders, and in several hereditary conditions (7, 37). The TGF-β superfamily ligands elicit their pleiotropic effects by signaling to the nucleus and inducing new programs of gene expression. The large number of ligands in this superfamily signal to the nucleus through a much smaller number of receptors and Smads, which act as intracellular signal transducers (14). Thus, different ligands utilize common pathway components. This raises important questions about how cells respond specifically to individual ligands and how cells integrate and interpret signals received from multiple ligands ...

Treatment with 0.4mg/mL rhBMP-2 resulted in significant growth changes and fusion of the coronal sutures bilaterally, anterior sagittal suture, and frontonasal suture by cephalometric analyses at 42 days postoperatively (p,0.05). Growth changes appeared greatest in the nasal region and less in the bicoronal and anterior sagittal regions. No significant differences in cranial growth were noted with use of 100-ug/mL biopatterned rhBMP-2 when compared to the empty defect group. Qualitative uCT analysis revealed comparable bony defect healing between rhBMP-2 groups. Application of high-dose, 0.4mg/mL rhBMP-2 resulted in pansynostosis upon uCT analysis, further verifying cranial growth restriction. Low-dose, 100-ug/mL biopatterned rhBMP-2 consistently regenerated bone within the surgical defect margin without evidence of extra-sutural invasion ...

TY - JOUR. T1 - Differential regulation of steroidogenesis by bone morphogenetic proteins in granulosa cells. T2 - Involvement of extracellularly regulated kinase signaling and oocyte actions in follicle-stimulating hormone-induced estrogen production. AU - Miyoshi, Tomoko. AU - Otsuka, Fumio. AU - Inagaki, Kenichi. AU - Otani, Hiroyuki. AU - Takeda, Masaya. AU - Suzuki, Jiro. AU - Goto, Junko. AU - Ogura, Toshio. AU - Makino, Hirofumi. PY - 2007. Y1 - 2007. N2 - In the present study, we investigated the cellular mechanism by which oocytes and bone morphogenetic proteins (BMPs) govern FSH-induced steroidogenesis using rat primary granulosa cells. BMP-6 and BMP-7 both inhibited FSH- and forskolin (FSK)-induced progesterone synthesis and reduced cAMP synthesis independent of the presence or absence of oocytes. BMP-7 also increased FSH-induced estradiol production, and the response was further augmented in the presence of oocytes. In contrast, BMP-6 had no impact on estradiol synthesis regardless ...

Specifically, Becky says she works on a Bone Morphogenic Protein pathway that is important for proper synaptic development in Drosophila larvae. My project focuses on how the active pathway is transported from the synaptic terminal to the neuron nucleus where gene transcription can take place. An implication of my research is towards neurodegenerative diseases where neuron survival signals are not able to reach the nucleus, causing the neuron to die. Also, discovering the basics of synaptic remodeling has larger implications on how synapses are strengthened during learning.. The awards and honors Becky has received since attending UAB are the UAB Medical Alumni Associations Carmichael Scholarship; 1st place in life sciences-session 2 at the 2006 UAB Graduate Student Research Days; 2nd place presentation at the 2006 UAB Cell Biology retreat; and 2nd place in life sciences-session 9 at the 2008 UAB Graduate Student Research Days. Although these accomplishments are impressive, her most rewarding ...

Specifically, Becky says she works on a Bone Morphogenic Protein pathway that is important for proper synaptic development in Drosophila larvae. My project focuses on how the active pathway is transported from the synaptic terminal to the neuron nucleus where gene transcription can take place. An implication of my research is towards neurodegenerative diseases where neuron survival signals are not able to reach the nucleus, causing the neuron to die. Also, discovering the basics of synaptic remodeling has larger implications on how synapses are strengthened during learning.. The awards and honors Becky has received since attending UAB are the UAB Medical Alumni Associations Carmichael Scholarship; 1st place in life sciences-session 2 at the 2006 UAB Graduate Student Research Days; 2nd place presentation at the 2006 UAB Cell Biology retreat; and 2nd place in life sciences-session 9 at the 2008 UAB Graduate Student Research Days. Although these accomplishments are impressive, her most rewarding ...

Bone morphogenetic protein 10 (BMP10) is a member of the TGF-β superfamily and plays a critical role in heart development. In the postnatal heart, BMP10 is restricted to the right atrium. The inactive pro-BMP10 (∼60 kDa) is processed into active BMP10 (∼14 kDa) by an unknown protease. Proteolytic cleavage occurs at the RIRR(316)↓ site (human), suggesting the involvement of proprotein convertase(s) (PCs). In vitro digestion of a 12-mer peptide encompassing the predicted cleavage site with furin, PACE4, PC5/6, and PC7, showed that furin cleaves the best, whereas PC7 is inactive on this peptide. Ex vivo studies in COS-1 cells, a cell line lacking PC5/6, revealed efficient processing of pro-BMP10 by endogenous PCs other than PC5/6. The lack of processing of overexpressed pro-BMP10 in the furin- and PACE4-deficient cell line, CHO-FD11, and in furin-deficient LoVo cells, was restored by stable (CHO-FD11/Fur cells) or transient (LoVo cells) expression of furin. Use of cell-permeable and cell surface

Background It has been reported that calf oocytes are less developmentally competent than oocytes obtained from adult cows. Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor...

Low-intensity pulsed ultrasound (LIPUS) is a safe and well-established therapeutic modality that is frequently used to accelerate fracture healing without surgical invasion. This modality is a source of mechanical energy transmitted as acoustic pressure waves into biological tissues, which subsequently evoke biochemical events that regulate fracture healing. Many clinical and experimental studies have shown that LIPUS stimulates the differentiation of a variety of cells, including osteoblasts and bone marrow stromal cells, thus enhancing bone regeneration by upregulating various cytokines and growth factors. However, the mechanisms by which LIPUS acts on osteoblasts and bone healing remain unclear. Bone morphogenetic proteins (BMPs) are well-known cytokines that play important roles in osteogenesis. These cytokines were originally discovered based on their ability to induce bone formation. Of the over 20 different isoforms of BMP described to date, three members of the BMP family, BMP-2, BMP-4, ...

Bone morphogenetic proteins (BMP) are thought to be important in breast cancer promotion and progression. We evaluated genetic variation in BMP-related genes and breast cancer risk among Hispanic (2,111 cases, 2,597 controls) and non-Hispanic White (NHW) (1,481 cases, 1,586 controls) women who participated in the 4-Corner's Breast Cancer Study, the Mexico Breast Cancer Study and the San Francisco Bay Area Breast Cancer Study. BMP genes and their receptors evaluated include ACVR1, AVCR2A, ACVR2B, ACVRL1, BMP1, BMP2, BMP4, BMP6, BMP7, BMPR1A, BMPR1B, BMPR2, MSTN and GDF10. Additionally, 104 ancestral informative markers were assessed to discriminate between European and native American ancestry. The importance of estrogen on BMP-related associations was suggested through unique associations by menopausal status and estrogen (ER) and progesterone (PR) receptor status of tumors. After adjustment for multiple comparisons ACVR1 (8 SNPs) was modestly associated with ER+PR+ tumors [odds ratios ...

TY - JOUR. T1 - 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein. AU - Shen, Hui. AU - Luo, Yu. AU - Kuo, Chi Chung. AU - Deng, Xiaolin. AU - Fang, Chen Fu. AU - Harvey, Brandon K.. AU - Hoffer, Barry J.. AU - Wang, Yun. PY - 2009/2/1. Y1 - 2009/2/1. N2 - Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral cortex at 24 hr after injection. Rats were also subjected to transient focal ...

article{68313ef7-27fc-4663-8f97-88e1ccb5049b, abstract = {The central role of bone morphogenetic proteins (BMPs) in the remodelling process of the human skeleton has been identified in numerous experimental and clinical studies. BMPs appear to be key agents in the osteoblastic differentiation of mesenchymal stem cells, and more recent evidence implicates them with the cells of the osteoclastic lineage. BMP-2, BMP-4, BMP-6 and BMP-7 have been studied in the context of osteoporosis and have been associated with its pathophysiological pathways. The theoretical advantages of local or systemic treatment of osteoporotic fractures with BMPs include the potential of inducing a rapid increase in bone strength locally at the fractured area and systemically in the entire skeleton, as well as accelerating the bone-healing period. Animal models of osteoporotic fractures suggested that the induction of new bone by local or systemic use of BMP-7 should be investigated as potential bone augmentation therapy to ...

TY - JOUR. T1 - Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis. AU - Xiao, Changchun. AU - Shim, Jae Hyuck. AU - Klüppel, Michael. AU - Zhang, Samuel Shao Min. AU - Dong, Chen. AU - Flavell, Richard A.. AU - Fu, Xin Yuan. AU - Wrana, Jeffrey L.. AU - Hogan, Brigid L M. AU - Ghosh, Sankar. PY - 2003/12/1. Y1 - 2003/12/1. N2 - Bone morphogenetic proteins (Bmps) are members of the transforming growth factor β (TGFβ) superfamily that play critical roles during mouse embryogenesis. Signaling by Bmp receptors is mediated mainly by Smad proteins. In this study, we show that a targeted null mutation of Ecsit, encoding a signaling intermediate of the Toll pathway, leads to reduced cell proliferation, altered epiblast patterning, impairment of mesoderm formation, and embryonic lethality at embryonic day 7.5 (E7.5), phenotypes that mimic the Bmp receptor type1a (Bmpr1a) null mutant. In addition, specific Bmp target gene expression is abolished in the absence of ...

Dr Edmond Bedrossian uses bone morphogenic protein to stimulate the cells to produce new bone during bone grafting surgery in San Francisco. 415-956-6610

Sample request, please email : [email protected] Summary Report Summary The United States Bone Morphogenetic Protein (BMP) 2 Industry 2017 Market

Author(s): Wang, Weiguang; Rigueur, Diana; Lyons, Karen M | Abstract: The ligands that comprise the Transforming Growth Factor β superfamily highly govern the development of the embryonic growth plate. Members of this superfamily activate canonical TGFβ and/or BMP (Bone Morphogenetic Protein) signaling pathways. How these pathways interact with one another is an area of active investigation. These two signaling pathways have been described to negatively regulate one another through crosstalk involving Smad proteins, the primary intracellular effectors of canonical signaling. More recently, a mechanism for regulation of the BMP pathway through TGFβ and BMP receptor interactions has been described. Here in this review, we demonstrate examples of how TGFβ is a gatekeeper of BMP action in the developing growth plate at both the receptor and transcriptional levels.

Influence of bone morphogenetic protein on articular cartilage regeneration following periosteal grafting. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Bone morphogenetic protein 2 opposes Shh-mediated proliferation in cerebellar granule cells through a TIEG-1-based regulation of Nmyc.

BACKGROUNDOsteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7), a member of the transforming growth factor-beta superfamily, has been shown to prevent kidney damage from ischemia/reperfusion injury in rats. The molecular events involved in OP-1 action on kidney are not yet understood.METHODSIn this study, we evaluated the biodistribution of (125)I-labeled OP-1 in rat kidneys. Adult rats received a single intravenous injection of 250 microg (125)I-labeled OP-1 per kg body wt, a dose that was effective in protecting kidneys from ischemic injury. Tissue localization, in situ hybridization, and immunostaining with a specific receptor antibody were performed to identify OP-1 cellular targets. Also, isolated plasma membranes from kidney cortex and medulla regions were analyzed to identify and characterize receptor structural components that recognize OP-1.RESULTSAt 10 and 180 minutes following injection, the relative uptake of (125)I-labeled OP-1 was consistently higher in kidney cortex than ...

DescriptionDevelopment is controlled by a surprisingly small number of genetic pathways. One such pathway is called the bone morphogenetic protein (BMP) pathway, similar from flies to humans. We used the common fruit fly, Drosophila melanogaster, to study the BMP pathway during Drosophila oogenesis, the formation of the egg. While the pathway is relatively simple, there exist combinations between the three different ligands, and four different receptors. My work focused largely on the two type II receptor, specifically on Wishful thinking (WIT). Much is known about the dynamic expression of the type I receptor during oogenesis, Thickveins. However, the pathway requires action of both type I and type II receptors. We found that WIT performs a necessary role during oogenesis and is regulated, indirectly, by BMP signaling. WIT is required for proper patterning of pathway target genes and necessary for proper formation of the eggshell. We also used a new technology, CRISPR/Cas9, to specifically ...

Establishment of mesodermal tissues in the amphibian body involves a series of inductive interactions probably elicited by a variety of peptide growth factors. Results reported here suggest that mesodermal patterning involves an array of signalling molecules including DVR-4, a TGF-beta-like molecule. We show that ectopic expression of DVR-4 causes embryos to develop with an overall posterior and/or ventral character, and that DVR-4 induces ventral types of mesoderm in animal cap explants. Moreover, DVR-4 overrides the dorsalizing effects of activin. DVR-4 is therefore the first molecule reported both to induce posteroventral mesoderm and to counteract dorsalizing signals such as activin. Possible interactions between these molecules resulting in establishment of the embryonic body plan are discussed.. ...

Objective: Pancreas organogenesis is orchestrated by interactions between the epithelium and the mesenchyme, but these interactions are incompletely understood. Here we investigated a role for BMP signalling within the pancreas mesenchyme and found it to be required for the normal development of the mesenchyme as well as the pancreatic epithelium.. Research Design and Methods: We analysed active BMP signalling by immunostaining for phospho-Smad1,5,8 and tested whether pancreas development was affected by BMP inhibition after expression of Noggin and dominant negative BMP receptors in chicken and mouse pancreas.. Results: Endogenous BMP signalling is confined to the mesenchyme in the early pancreas and inhibition of BMP signalling results in severe pancreatic hypoplasia with reduced epithelial branching. Notably, we also observe an excessive endocrine differentiation when mesenchymal BMP signalling is blocked, presumably secondary to defective mesenchyme to epithelium signalling.. Conclusions: We ...

Research Interests: Signal Transduction Bone Morphogenetic Proteins Growth and Embryonic Development Mouse Models Xenopus laevis Proprotein Convertases Hematopoiesis Extracellular Matrix Cell-cell signaling molecules such as bone morphogenetic proteins (BMPs) play critical roles in specifying cell fate during vertebrate embryogenesis. Strict regulation of BMP activity is required to prevent birth defects, degenerative diseases and cancer. Our research program has two major foci: 1) Understanding how BMP activity is regulated by cleavage of the precursor protein and by interactions with the extracellular matrix. We use targeted mutagenesis in mice together with cell biological and biochemical approaches in Xenopus embryos to determine how cleavages within the inactive prodomain of the BMP precursor protein regulate the activity of mature BMP homodimers and heterodimers. One current project in the lab involves analysis of mice carrying a point mutation that prevents cleavage of BMP7. This cleavage ...

In vitro studies using the myogenic cell line C2C12 demonstrate that bone morphogenetic protein-2 (BMP-2) converts the developmental pathway of C2C12 from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo studies using null mutation mice demonstrate that BMPs inhibit the specification of the developmental fate of myogenic progenitor cells. However, the roles of BMPs in the phases of differentiation and maturation in skeletal muscles have yet to be determined. The present study attempts to define the function of BMP-2 in the final stage of differentiation of mouse tongue myoblast. Recombinant BMP-2 inhibited the expressions of markers for the differentiation of skeletal muscle cells, such as myogenin, muscle creatine kinase (MCK), and fast myosin heavy chain (fMyHC), whereas BMP-2 siRNA stimulated such markers. Neither the recombinant BMP-2 nor BMP-2 siRNA altered the expressions of markers for the formation of cartilage and bone, such as osteocalcin, alkaline phosphatase (ALP),

Yu focuses on bone morphogenetic proteins (BMP) - groups of signaling molecules that are vital to tissue development - and how a BMP receptor mutation signals the body to grow bone where it does not belong. Yu and his team tried to recreate the disease in mouse models to gain more insight into how it occurs and its cells of origin. Though targeting bone marrow and several blood vessel-associated cells in mice with the mutation did not produce the intended result, focusing on other types of cells did.. Targeting expression of the mutant receptor to skeletal muscle interstitial cells - the cells that lie between muscle fiber cells - didnt immediately produce bone formation, but once there was an injury to the muscle, bone began to develop.. This was very reminiscent of some of the observations we had from people who experienced the replacement of muscle tissue with bone following injury, said Yu.. When the team targeted expression of the mutant receptor to tendon and ligament cells of mice, ...

Chondrogenic differentiating mesenchymal stem cells (MSCs) are mimicking embryonal endochondral ossification and become hypertrophic. BMP (bone morphogenetic protein) and Activin Membrane Bound Inhibitor (BAMBI) is a pseudoreceptor that regulates the activity of transforming growth factor-|i|β|/i| (TGF-|i|β|/i|) and BMP signalling during chondrogenesis. Both TGF-|i|β|/i| and BMP signalling are regulators of chondrogenic cell differentiation. Human bone marrow derived MSCs were chondrogenically predifferentiated in aggregate culture for 14 days. Thereafter, one group was subjected to hypertrophy enhancing media conditions while controls were kept in chondrogenic medium until day 28. Histological evaluation, gene expression by PCR, and Western blot analysis were carried out at days 1, 3, 7, 14, 17, 21, and 28. A subset of cultures was treated with the BMP inhibitor Noggin to test for BMP dependent expression of BAMBI. Hypertrophic differentiated pellets showed larger cells with increased

Chambered cover glass /Glass bottom dishes / glass bottom plates at Cellvis (formerly In Vitro Scientific) for confocal microscopy studies. ideal for fluorescence microscopy.

We next investigated the possible role of Bmp6 in the induction of hepcidin by inflammation. Hepcidin is part of the type II acute-phase response and is thought to have a crucial role in anemia of chronic disease. Whereas hepcidin is induced by activation of the inflammatory pathway in Hfe2-deficient mice(14), this induction is not observed in mice with liver-specific Smad4 deficiency(11). We therefore set out to determine whether lipopolysaccharide (LPS)-dependent induction of hepcidin requires Bmp6 by treating Bmp6 mutant mice and wild-type controls with LPS or saline solution. As expected, the acute-phase genes Il6, Tnf and Crp were strongly induced in LPS-treated mice as compared with saline-treated animals (see Supplementary Figs. 6 and 7 online). Hamp gene expression was induced about 24-fold in response to the LPS treatment in Bmp6 -/- mice and 2.6-fold in wild-type controls (Fig. 1). Notably, Hamp mRNA levels in LPS- injected Bmp6 -/- animals did not reach those of wild-type controls. ...

Purpose.: There are limited studies on the factors that regulate the processing of TGF-β2 and extracellular matrix (ECM) proteins into their mature form. Bone morphogenic protein 1 (BMP1) is an enzyme responsible for the cleavage and maturation of growth factors and ECM proteins. The purpose of our study was to determine whether cultured human trabecular meshwork (TM) cells express BMP1, BMP1 expression is regulated by TGF-β2, BMP1 is biologically active, and BMP1 regulates LOX activity. Methods.: Primary human TM cells were isolated and subjected to quantitative PCR (qPCR) and Western immunoblotting (WB) for BMP1. BMP1 immunolocalization was performed in TM tissues. qPCR was used to determine BMP1 mRNA expression and WB results were used to determine BMP1 protein expression. BMP1 activity was measured in TM cells treated with TGF-β2 or with a combination of TGF-β2/UK383367. Lysyl oxidase (LOX) enzyme activity was evaluated by WB in TM cells treated with BMP1 or with a combination of ...

A composition comprising a pharmaceutically acceptable admixture of an osteogenic protein; a polymer matrix component selected from the group consisting of poly(lactic acid), poly(glycolic acid), and copolymers of lactic acid and glycolic acid; and an osteogenic protein-sequestering material.

FGF-10 is involved in the initial budding as well as the continuous outgrowth of vertebrate limbs, FGF10 mRNA is expressed preferentially in neurons but not in glial cells and may have a distinct role in the brain. human FGF-10 is mitogenic for fetal rat keratinizing epidermal cells but not for NIH 3T3 cells.Recombinant FGF10 induces the proliferation of human urothelial cells in vitro and induces the proliferation of transitional epithelium. FGF-10 is secreted by cultured mouse pre-adipocytes, prevention of FGF-10 signaling inhibits subsequent differentiation. The ability of embryonic fibroblasts derived from FGF-10 knock-out mice to differentiate into adipocytes is also impaired.

Key Points. Endothelial Bmp6 conditional knockout mice exhibit hemochromatosis, whereas hepatocyte and macrophage Bmp6 conditional knockout mice do not.Our data

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Pediatric neuroblastoma in its advanced stage (st. IV) is usually lethal. 70% of the affected children die. 50% of the children show upon diagnosis metastasis or a genetic amplification of the oncogene N-myc. This group has a poor prognosis and a 5-year survival rate of only 33%. A drawback of the current standard therapy is the poor efficacy accompanied with severe side effects. Therefore a new treatment of neuroblastoma with a different antitumoral mode of action than the traditional cytotoxics is urgently required ...

Fingerprint Dive into the research topics of Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-β superfamily predominantly expressed in long bones during human embryonic development. Together they form a unique fingerprint. ...