Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.Bone Morphogenetic Protein 4: A bone morphogenetic protein that is a potent inducer of bone formation. It also functions as a regulator of MESODERM formation during EMBRYONIC DEVELOPMENT.Bone Morphogenetic Protein 7: A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.Bone Morphogenetic Protein Receptors, Type I: A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.Bone Morphogenetic Protein Receptors: A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS. They are PROTEIN-SERINE-THREONINE KINASES that mediate SIGNAL TRANSDUCTION PATHWAYS through SMAD PROTEINS.Bone Morphogenetic Protein 6: A bone morphogenetic protein that is a potent inducer of BONE formation. It plays additional roles in regulating CELL DIFFERENTIATION of non-osteoblastic cell types and epithelial-mesenchymal interactions.Bone Morphogenetic Protein Receptors, Type II: A subtype of bone morphogenetic protein receptors with low affinity for BONE MORPHOGENETIC PROTEINS. They are constitutively active PROTEIN-SERINE-THREONINE KINASES that can interact with and phosphorylate TYPE I BONE MORPHOGENETIC PROTEIN RECEPTORS.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Bone Morphogenetic Protein 5: A bone morphogenetic protein that may play a role in CARTILAGE formation. It is a potent regulator of the growth of CHONDROCYTES and the synthesis of cartilage matrix proteins. Evidence for its role in cartilage formation can be seen in MICE, where genetic mutations that cause loss of bone morphogenetic protein 5 function result in the formation of small malformed ears.Smad1 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and plays an essential role in EMBRYONIC DEVELOPMENT.Smad Proteins: A family of proteins that are involved in the translocation of signals from TGF-BETA RECEPTORS; BONE MORPHOGENETIC PROTEIN RECEPTORS; and other surface receptors to the CELL NUCLEUS. They were originally identified as a class of proteins that are related to the mothers against decapentaplegic protein, Drosophila and sma proteins from CAENORHABDITIS ELEGANS.Bone Morphogenetic Protein 3: A bone morphogenetic protein that is found at high concentrations in a purified osteoinductive protein fraction from BONE. Bone morphogenetic protein 3 is referred to as osteogenin, however it may play a role in variety of developmental processes.Smad5 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and is essential for PHYSIOLOGICAL ANGIOGENESIS.Bone Morphogenetic Protein 15: A protein that plays a role in GRANULOSA CELLS where it regulates folliculogenesis. Mutations in the gene for bone morphogenetic protein 15 are linked to reproductive abnormalities such as PREMATURE OVARIAN FAILURE.Bone Morphogenetic Protein 1: A bone morphogenetic protein family member that includes an active tolloid-like metalloproteinase domain. The metalloproteinase activity of bone morphogenetic protein 1 is specific for the removal of the C-propeptide of PROCOLLAGEN and may act as a regulator of EXTRACELLULAR MATRIX deposition. Alternative splicing of MRNA for bone morphogenetic protein 1 results in the production of several PROTEIN ISOFORMS.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Bone Remodeling: The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.Smad6 Protein: An inhibitory Smad protein that negatively regulates the SIGNAL TRANSDUCTION PATHWAYS from BONE MORPHOGENETIC PROTEIN RECEPTORS. Smad6 inhibits PHOSPHORYLATION of SMAD2 PROTEIN and SMAD3 PROTEIN.Smad8 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS and regulates BONE MORPHOGENETIC PROTEIN signaling.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Osteogenesis: The process of bone formation. Histogenesis of bone including ossification.Growth Differentiation Factor 2: A growth differentiation factor that plays a regulatory role as a paracrine factor for a diverse array of cell types during EMBRYONIC DEVELOPMENT and in the adult tissues. Growth differentiation factor 2 is also a potent regulator of CHONDROGENESIS and was previously referred to as bone morphogenetic protein 9.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Osteoblasts: Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.Bone Regeneration: Renewal or repair of lost bone tissue. It excludes BONY CALLUS formed after BONE FRACTURES but not yet replaced by hard bone.Bone Density: The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.Receptors, Growth Factor: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.Growth Differentiation Factors: A family of BONE MORPHOGENETIC PROTEIN-related proteins that are primarily involved in regulation of CELL DIFFERENTIATION.Growth Differentiation Factor 5: A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.Bone Development: The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Growth Differentiation Factor 9: A bone morphogenetic protein that plays an essential role in the regulation of ovarian folliculogenesis.Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.Bone Resorption: Bone loss due to osteoclastic activity.Activin Receptors, Type I: One of the two types of ACTIVIN RECEPTORS or activin receptor-like kinases (ALK'S). There are several type I activin receptors. The major active ones are ALK-2 (ActR-IA) and ALK-4 (ActR-IB).Growth Differentiation Factor 6: A growth differentiation factor that plays a role in the neural differentiation, specifically in the retinal development of the EYE.Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Smad4 Protein: A signal transducing adaptor protein and tumor suppressor protein. It forms a complex with activated RECEPTOR-REGULATED SMAD PROTEINS. The complex then translocates to the CELL NUCLEUS and regulates GENETIC TRANSCRIPTION of target GENES.Bone Neoplasms: Tumors or cancer located in bone tissue or specific BONES.Activin Receptors, Type II: One of the two types of ACTIVIN RECEPTORS. They are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES. The major type II activin receptors are ActR-IIA and ActR-IIB.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Diseases: Diseases of BONES.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Follistatin: A broadly distributed protein that binds directly to ACTIVINS. It functions as an activin antagonist, inhibits FOLLICLE STIMULATING HORMONE secretion, regulates CELL DIFFERENTIATION, and plays an important role in embryogenesis. Follistatin is a single glycosylated polypeptide chain of approximately 37-kDa and is not a member of the inhibin family (INHIBINS). Follistatin also binds and neutralizes many members of the TRANSFORMING GROWTH FACTOR BETA family.Body Patterning: The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.Mesoderm: The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.Activin Receptors: Receptors for ACTIVINS are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES, thus also named activin receptor-like kinases (ALK's). Activin receptors also bind TRANSFORMING GROWTH FACTOR BETA. As those transmembrane receptors of the TGF-beta superfamily (RECEPTORS, TRANSFORMING GROWTH FACTOR BETA), ALK's consist of two different but related protein kinases, Type I and Type II. Activins initiate cellular signal transduction by first binding to the type II receptors (ACTIVIN RECEPTORS, TYPE II ) which then recruit and phosphorylate the type I receptors (ACTIVIN RECEPTORS, TYPE I ) with subsequent activation of the type I kinase activity.Inhibitor of Differentiation Protein 1: A negative regulator of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS that blocks activation of CYCLIN-DEPENDENT KINASE INHIBITOR P16 and is de-regulated in a variety of NEOPLASMS.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Smad Proteins, Receptor-Regulated: A family of smad proteins that undergo PHOSPHORYLATION by CELL SURFACE RECEPTORS in response to TRANSFORMING GROWTH FACTOR BETA; ACTIVIN; or BONE MORPHOGENETIC PROTEIN signaling.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.Tolloid-Like Metalloproteinases: A family of metalloproteases that are related to the DROSOPHILA protein tolloid, which is a gene product necessary for dorsal-ventral patterning in early Drosophila embryogenesis. Many members of the group may play a significant role in intercellular signaling.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Bone Transplantation: The grafting of bone from a donor site to a recipient site.MSX1 Transcription Factor: A homeodomain protein that interacts with TATA-BOX BINDING PROTEIN. It represses GENETIC TRANSCRIPTION of target GENES and plays a critical role in ODONTOGENESIS.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Xenopus Proteins: Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.Ossification, Heterotopic: The development of bony substance in normally soft structures.Core Binding Factor Alpha 1 Subunit: A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION.Chondrogenesis: The formation of cartilage. This process is directed by CHONDROCYTES which continually divide and lay down matrix during development. It is sometimes a precursor to OSTEOGENESIS.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.Hypertension, Pulmonary: Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Myositis Ossificans: A disease characterized by bony deposits or the ossification of muscle tissue.Smad7 Protein: An inhibitory smad protein that associates with TRANSFORMING GROWTH FACTOR BETA RECEPTORS and BONE MORPHOGENETIC PROTEIN RECEPTORS. It negatively regulates SIGNAL TRANSDUCTION PATHWAYS by inhibiting PHOSPHORYLATION of RECEPTOR-REGULATED SMAD PROTEINS.Hedgehog Proteins: A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.Bone Substitutes: Synthetic or natural materials for the replacement of bones or bone tissue. They include hard tissue replacement polymers, natural coral, hydroxyapatite, beta-tricalcium phosphate, and various other biomaterials. The bone substitutes as inert materials can be incorporated into surrounding tissue or gradually replaced by original tissue.Wnt Proteins: Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.Hepcidins: Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.Chondrocytes: Polymorphic cells that form cartilage.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Ectoderm: The outer of the three germ layers of an embryo.Morphogenesis: The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Skull: The SKELETON of the HEAD including the FACIAL BONES and the bones enclosing the BRAIN.Mice, Inbred C57BLEmbryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Wnt3A Protein: A Wnt protein subtype that plays a role in cell-cell signaling during EMBRYONIC DEVELOPMENT and the morphogenesis of the developing NEURAL TUBE.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Mesenchymal Stromal Cells: Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Receptors, Transforming Growth Factor beta: Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.Fractures, Bone: Breaks in bones.Bone Diseases, MetabolicMice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Embryo, Mammalian: The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.Wnt3 Protein: A Wnt protein subtype that plays a role in cell-cell signaling during EMBRYONIC DEVELOPMENT and the morphogenesis of the developing NEURAL TUBE. Defects in Wnt3 protein are associated with autosomal recessive tetra-AMELIA in humans.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Bone Marrow Transplantation: The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Smad2 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. It regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes BONY CALLUS formation and normal replacement of bone tissue.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Periosteum: Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.Neural Crest: The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.Nodal Protein: The founding member of the nodal signaling ligand family of proteins. Nodal protein was originally discovered in the region of the mouse embryo primitive streak referred to as HENSEN'S NODE. It is expressed asymmetrically on the left side in chordates and plays a critical role in the genesis of left-right asymmetry during vertebrate development.X-Ray Microtomography: X-RAY COMPUTERIZED TOMOGRAPHY with resolution in the micrometer range.Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Embryonic Stem Cells: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Gastrula: The developmental stage that follows BLASTULA or BLASTOCYST. It is characterized by the morphogenetic cell movements including invagination, ingression, and involution. Gastrulation begins with the formation of the PRIMITIVE STREAK, and ends with the formation of three GERM LAYERS, the body plan of the mature organism.Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee.Embryonic Induction: The complex processes of initiating CELL DIFFERENTIATION in the embryo. The precise regulation by cell interactions leads to diversity of cell types and specific pattern of organization (EMBRYOGENESIS).Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Limb Deformities, Congenital: Congenital structural deformities of the upper and lower extremities collectively or unspecified.Inhibins: Glycoproteins that inhibit pituitary FOLLICLE STIMULATING HORMONE secretion. Inhibins are secreted by the Sertoli cells of the testes, the granulosa cells of the ovarian follicles, the placenta, and other tissues. Inhibins and ACTIVINS are modulators of FOLLICLE STIMULATING HORMONE secretions; both groups belong to the TGF-beta superfamily, as the TRANSFORMING GROWTH FACTOR BETA. Inhibins consist of a disulfide-linked heterodimer with a unique alpha linked to either a beta A or a beta B subunit to form inhibin A or inhibin B, respectivelyGranulosa Cells: Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).Antimicrobial Cationic Peptides: Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Organogenesis: Formation of differentiated cells and complicated tissue organization to provide specialized functions.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).Extremities: The farthest or outermost projections of the body, such as the HAND and FOOT.Inhibin-beta Subunits: They are glycopeptides and subunits in INHIBINS and ACTIVINS. Inhibins and activins belong to the transforming growth factor beta superfamily.Transforming Growth Factor beta1: A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.Endoderm: The inner of the three germ layers of an embryo.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the FIBULA laterally, the TALUS distally, and the FEMUR proximally.Ulna: The inner and longer bone of the FOREARM.Bone Demineralization Technique: Removal of mineral constituents or salts from bone or bone tissue. Demineralization is used as a method of studying bone strength and bone chemistry.Paracrine Communication: Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS on surrounding cells.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Brachydactyly: Congenital anomaly of abnormally short fingers or toes.Inhibitor of Differentiation Proteins: Inhibitor of differentiation proteins are negative regulators of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS. They inhibit CELL DIFFERENTIATION and induce CELL PROLIFERATION by modulating different CELL CYCLE regulators.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Tissue Engineering: Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.Hair Follicle: A tube-like invagination of the EPIDERMIS from which the hair shaft develops and into which SEBACEOUS GLANDS open. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. (Stedman, 26th ed) Follicles of very long hairs extend into the subcutaneous layer of tissue under the SKIN.Growth Differentiation Factor 10: A growth differentiation factor that is closely-related in structure to BONE MORPHOGENETIC PROTEIN 3. Growth differentiation factor 10 is found at high levels in BONE, however it plays an additional roles in regulating EMBRYONIC DEVELOPMENT.beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Embryonic Development: Morphological and physiological development of EMBRYOS.Cell Line, Tumor: A cell line derived from cultured tumor cells.Fractures, Cartilage: Breaks in CARTILAGE.Osteocytes: Mature osteoblasts that have become embedded in the BONE MATRIX. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.DioxolesCartilage, Articular: A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.SOX9 Transcription Factor: A SOXE transcription factor that plays a critical role in regulating CHONDROGENESIS; OSTEOGENESIS; and male sex determination. Loss of function of the SOX9 transcription factor due to genetic mutations is a cause of CAMPOMELIC DYSPLASIA.Ovary: The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Odontogenesis: The process of TOOTH formation. It is divided into several stages including: the dental lamina stage, the bud stage, the cap stage, and the bell stage. Odontogenesis includes the production of tooth enamel (AMELOGENESIS), dentin (DENTINOGENESIS), and dental cementum (CEMENTOGENESIS).Myocytes, Smooth Muscle: Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).Follistatin-Related Proteins: Broadly distributed glycoproteins that are homologous to the activin-binding protein, FOLLISTATIN. These follistatin-related proteins are encoded by a number of genes.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.Nerve Tissue ProteinsStromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Fibroblast Growth Factor 8: A fibroblast growth factor that preferentially activates FIBROBLAST GROWTH FACTOR RECEPTOR 4. It was initially identified as an androgen-induced growth factor and plays a role in regulating growth of human BREAST NEOPLASMS and PROSTATIC NEOPLASMS.Culture Media, Conditioned: Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).Synostosis: A union between adjacent bones or parts of a single bone formed by osseous material, such as ossified connecting cartilage or fibrous tissue. (Dorland, 27th ed)Calcinosis: Pathologic deposition of calcium salts in tissues.Transforming Growth Factor beta3: A TGF-beta subtype that plays role in regulating epithelial-mesenchymal interaction during embryonic development. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta3 and TGF-beta3 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Osseointegration: The growth action of bone tissue as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants).Transforming Growth Factor beta2: A TGF-beta subtype that was originally identified as a GLIOBLASTOMA-derived factor which inhibits the antigen-dependent growth of both helper and CYTOTOXIC T LYMPHOCYTES. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta2 and TGF-beta2 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.Nervous System: The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)Ovarian Follicle: An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The number and size of follicles vary depending on the age and reproductive state of the female. The growing follicles are divided into five stages: primary, secondary, tertiary, Graafian, and atretic. Follicular growth and steroidogenesis depend on the presence of GONADOTROPINS.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Temporal Bone: Either of a pair of compound bones forming the lateral (left and right) surfaces and base of the skull which contains the organs of hearing. It is a large bone formed by the fusion of parts: the squamous (the flattened anterior-superior part), the tympanic (the curved anterior-inferior part), the mastoid (the irregular posterior portion), and the petrous (the part at the base of the skull).Cumulus Cells: The granulosa cells of the cumulus oophorus which surround the OVUM in the GRAAFIAN FOLLICLE. At OVULATION they are extruded with OVUM.Smad3 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. Activated Smad3 can bind directly to DNA, and it regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.OdontoblastsMice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Neurulation: An early embryonic developmental process of CHORDATES that is characterized by morphogenic movements of ECTODERM resulting in the formation of the NEURAL PLATE; the NEURAL CREST; and the NEURAL TUBE. Improper closure of the NEURAL GROOVE results in congenital NEURAL TUBE DEFECTS.Tissue Scaffolds: Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.

Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. (1/115)

In addition to pituitary gonadotropins and paracrine factors, ovarian follicle development is also modulated by oocyte factors capable of stimulating granulosa cell proliferation but suppressing their differentiation. The nature of these oocyte factors is unclear. Because growth differentiation factor-9 (GDF-9) enhanced preantral follicle growth and was detected in the oocytes of early antral and preovulatory follicles, we hypothesized that this oocyte hormone could regulate the proliferation and differentiation of granulosa cells from these advanced follicles. Treatment with recombinant GDF-9, but not FSH, stimulated thymidine incorporation into cultured granulosa cells from both early antral and preovulatory follicles, accompanied by increases in granulosa cell number. Although GDF-9 treatment alone stimulated basal steroidogenesis in granulosa cells, cotreatment with GDF-9 suppressed FSH-stimulated progesterone and estradiol production. In addition, GDF-9 cotreatment attentuated FSH-induced LH receptor formation. The inhibitory effects of GDF-9 on FSH-induced granulosa cell differentiation were accompanied by decreases in the FSH-induced cAMP production. These data suggested that GDF-9 is a proliferation factor for granulosa cells from early antral and preovulatory follicles but suppresses FSH-induced differentiation of the same cells. Thus, oocyte-derived GDF-9 could account, at least partially, for the oocyte factor(s) previously reported to control cumulus and granulosa cell differentiation.  (+info)

Expression of growth and differentiation factor-9 in the ovaries of fetal sheep homozygous or heterozygous for the inverdale prolificacy gene (FecX(I)). (2/115)

Abnormal follicular and oocyte growth in ovaries of sheep homozygous (II) for the Inverdale gene, FecX(I), suggest that this gene may influence a fundamental event in initiation of folliculogenesis, with two copies of the gene inhibiting growth at the primordial/primary stage. In addition, striking similarities in ovarian morphology between mice deficient in growth and differentiation factor-9 (GDF-9) and II sheep suggest a relationship between the FecX(I) gene and GDF-9 function in the ovary. Therefore, it was hypothesized that GDF-9 mRNA expression would be inhibited in ovaries of II fetal sheep. To test this hypothesis, in situ hybridization was used to characterize GDF-9 mRNA expression in ovaries of homozygous (II), heterozygous (I+), and control (++) fetal sheep at Day 135 of gestation. GDF-9 mRNA expression was localized exclusively to oocytes from the type 1 follicle stage onward in all genotypes and is the first demonstration of GDF-9 mRNA expression in ovaries of fetal sheep. In addition, GDF-9 mRNA expression was detected in oocytes of abnormal type 2 follicles in the ovaries of II sheep. Thus, it does not appear that inhibition of GDF-9 gene expression is the mechanism of action whereby the FecX(I) gene exerts its influence. However, the possibility of translation at specific stages of follicular development cannot presently be ruled out. In addition, the FecX(I) gene may be involved, either directly or indirectly, in regulating expression of receptors for GDF-9. At present, however, neither the FecX(I) gene product nor the GDF-9 receptor has been isolated or characterized.  (+info)

Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. (3/115)

Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor beta superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin E(2) (PGE(2)) receptor (EP2; Ptgerep2) are required for fertility in female but not male mice. To define the interrelationship of these factors, we used a preovulatory granulosa cell culture system in which we added recombinant GDF-9, prostaglandins, prostaglandin receptor agonists, or cyclooxygenase inhibitors. GDF-9 stimulated Cox2 mRNA within 2 h, and PGE(2) within 6 h; however, progesterone was not increased until 12 h after addition of GDF-9. This suggested that Cox2 is a direct downstream target of GDF-9 but that progesterone synthesis required an intermediate. To determine whether prostaglandin synthesis was required for progesterone production, we analyzed the effects of PGE(2) and cyclooxygenase inhibitors on this process. PGE(2) can stimulate progesterone synthesis by itself, although less effectively than GDF-9 (3-fold vs. 6-fold increase over 24 h, respectively). Furthermore, indomethacin or NS-398, inhibitors of Cox2, block basal and GDF-9-stimulated progesterone synthesis. However, addition of PGE(2) to cultures containing both GDF-9 and NS-398 overrides the NS-398 block in progesterone synthesis. To further define the PGE(2)-dependent pathway, we show that butaprost, a specific EP2 agonist, stimulates progesterone synthesis and overrides the NS-398 block. In addition, GDF-9 stimulates EP2 mRNA synthesis by a prostaglandin- and progesterone-independent pathway. Thus, GDF-9 induces an EP2 signal transduction pathway which appears to be required for progesterone synthesis in cumulus granulosa cells. These studies further demonstrate the importance of oocyte-somatic cell interactions in female reproduction.  (+info)

Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis. (4/115)

Growth differentiation factor-9 (GDF-9) was shown recently to be essential for early follicular development, including the appearance of the theca layer. Theca cells provide the androgen substrate for aromatization and estrogen production by granulosa cells. Using biologically active recombinant GDF-9 (rGDF-9) and an androgen-producing immortalized theca-interstitial cell (TIC) line or primary TIC, we have examined the action of this paracrine hormone on theca cell steroidogenesis. The effect of GDF-9 on TIC progesterone synthesis was marginal and inconsistent in the primary cultures. In immortalized theca cells, GDF-9 attenuated the forskolin-stimulated progesterone accumulation. More significantly, this oocyte-derived growth factor enhanced both basal and stimulated androstenedione accumulation in the primary and transformed TIC cultures. The effects of GDF-9 on steroidogenesis by preovulatory follicles were relatively modest. Likewise, it did not affect the maturation of follicle-enclosed oocytes. The effect of GDF-9, an oocyte product, on TIC androgen production suggests a regulatory role of the oocyte on theca cell function and hence on follicle development and differentiation. This direct effect of GDF-9 on thecal steroidogenesis is consistent with its recently demonstrated actions on thecal cell recruitment and differentiation.  (+info)

Bone morphogenetic protein-15. Identification of target cells and biological functions. (5/115)

In developing ovarian follicles, the regulation of cell proliferation and differentiation is tightly coordinated. Precisely how this coordination is achieved is unknown, but recent observations have suggested that molecules emitted by the oocyte are involved in the process. The newly discovered oocyte-specific growth factor, bone morphogenetic protein-15 (BMP-15), is one such molecule. At present, nothing is known about the target cells and biological functions of BMP-15. To fill this gap in our knowledge, recombinant BMP-15 and its antibody were produced and used to determine BMP-15 expression and bioactivity. BMP-15 mRNA and protein were shown to be co-expressed in oocytes throughout folliculogenesis, supporting the idea that BMP-15 is a physiological regulator of follicle cell proliferation and/or differentiation. To test this, we used primary cultures of rat granulosa cells (GCs). We found that BMP-15 is a potent stimulator of GC proliferation, and importantly, the mitogenic effect was follicle-stimulating hormone (FSH)-independent. By contrast, BMP-15 alone had no effect on steroidogenesis. However, it produced a marked decrease in FSH-induced progesterone production, but had no effect on FSH-stimulated estradiol production. This result indicates that BMP-15 is a selective modulator of FSH action. In summary, this study identifies GCs as the first target cells for BMP-15. Moreover, it identifies the stimulation of GC proliferation and the differential regulation of two crucial steroid hormones as the first biological functions of BMP-15. Significantly, BMP-15 is the first growth factor that can coordinate GC proliferation and differentiation in a way that reflects normal physiology.  (+info)

Comparison of recombinant growth differentiation factor-9 and oocyte regulation of KIT ligand messenger ribonucleic acid expression in mouse ovarian follicles. (6/115)

Oocytes secrete factors that regulate the development of the surrounding granulosa cells in ovarian follicles. KIT ligand (KL) mRNA expression in granulosa cells is thought to be regulated by oocytes; however, the factor(s) that mediate this effect are not known. One candidate is the oocyte-specific gene product growth differentiation factor-9 (GDF-9). This study examined the effect of recombinant GDF-9 (rGDF-9) on steady-state KL mRNA expression levels in preantral and mural granulosa cells in vitro. Furthermore, the study compared the effect of rGDF-9 with that of coculture with oocytes at different developmental stages. As determined by RNase protection assay, both KL-1 and KL-2 mRNA levels in preantral and mural granulosa cells were suppressed by 25-250 ng/ml rGDF-9. Fully grown oocytes also suppressed both KL-1 and KL-2 mRNA expression levels. Partly grown oocytes isolated from 7-, 10-, or 12-day-old mice either had no effect on KL mRNA levels or promoted KL-1 mRNA steady-state expression. It is concluded that GDF-9 is likely to mediate the action of fully grown, but not partly grown, oocytes on granulosa cell KL mRNA expression.  (+info)

Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression. (7/115)

We have recently reported that oocyte-derived bone morphogenetic protein-15 (BMP-15) can directly modulate follicle-stimulating hormone (FSH) action in rat granulosa cells. Here, we investigate underlying mechanisms of this BMP-15 effect. Treatment with BMP-15 alone exerted no significant effect on the basal expression of mRNAs encoding steroidogenic acute regulatory protein, P450 side chain cleavage enzyme, P450 aromatase, 3beta-hydroxysteroid dehydrogenase, luteinization hormone receptor, and inhibin/activin subunits. However, BMP-15 markedly inhibited the FSH-induced increases in these messages. In striking contrast, BMP-15 did not change the forskolin-induced levels of these transcripts. Thus, the inhibitory effect of BMP-15 on FSH action must be upstream of cAMP signaling. We next examined changes in FSH receptor mRNA expression. Interestingly, BMP-15 severely reduced the levels of FSH receptor mRNA in both basal and FSH-stimulated cells. To determine whether this effect was at the level of FSH function, we investigated the effect of BMP-15 on FSH bioactivity. Consistent with the mRNA data, BMP-15 inhibited the biological response of FSH, but not that of forskolin. Based on these results, we propose that BMP-15 is an important determinant of FSH action through its ability to inhibit FSH receptor expression. Because FSH plays an essential role in follicle growth and development, our findings could have new implications for understanding how oocyte growth factors contribute to folliculogenesis.  (+info)

Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary. (8/115)

The process of ovarian folliculogenesis is composed of proliferation and differentiation of the constitutive cells in developing follicles. Growth factors emitted by oocytes integrate and promote this process. Growth differentiation factor-9 (GDF-9), bone morphogenetic protein (BMP)-15, and BMP-6 are oocyte-derived members of the transforming growth factor-beta superfamily. In contrast to the recent studies on GDF-9 and BMP-15, nothing is known about the biological function of BMP-6 in the ovary. Here we show that, unlike BMP-15 and GDF-9, BMP-6 lacks mitogenic activity on rat granulosa cells (GCs) and produces a marked decrease in follicle-stimulating hormone (FSH)-induced progesterone (P(4)) but not estradiol (E(2)) production, demonstrating not only the first identification of GCs as BMP-6 targets in the ovary but also its selective modulation of FSH action in steroidogenesis. This BMP-6 activity resembles BMP-15 but differs from GDF-9 activities. BMP-6 also exhibited similar action to BMP-15 by attenuating the steady state mRNA levels of FSH-induced steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage enzyme (P450scc), without affecting P450 aromatase mRNA level, supporting its differential function on FSH-regulated P(4) and E(2) production. However, unlike BMP-15, BMP-6 inhibited forskolin- but not 8-bromo-cAMP-induced P(4) production and StAR and P450scc mRNA expression. BMP-6 also decreased FSH- and forskolin-stimulated cAMP production, suggesting that the underlying mechanism by which BMP-6 inhibits FSH action most likely involves the down-regulation of adenylate cyclase activity. This is clearly distinct from the mechanism of BMP-15 action, which causes the suppression of basal FSH receptor (FSH-R) expression, without affecting adenylate cyclase activity. As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it inhibited FSH- and forskolin- but not 8-bromo-cAMP-induced FSH-R mRNA accumulation. These studies provide the first insight into the biological function of BMP-6 in the ovary and demonstrate its unique mechanism of regulating FSH action.  (+info)

Mol Hum Reprod. 2014 Jan 26. [Epub ahead of print] Chang HM, Cheng JC, Taylor E, Leung PC. Author information Abstract In the ovary, connexin-coupled gap junctions in granulosa cells play crucial roles in follicular and oocyte development as well as in corpus luteum formation. Our previous work has shown that theca cell-derived bone morphogenetic protein (BMP)4 and BMP7 decrease gap junction intercellular communication (GJIC) activity via the down-regulation of connexin43 (Cx43) expression in immortalized human granulosa cells. However, the effects of oocyte-derived growth factors on Cx43 expression remain to be elucidated. The present study was designed to investigate the effects of oocyte-derived growth differentiation factor (GDF)9 and BMP15 on the expression of Cx43 in a human granulosa cell line, SVOG. We also examined the effect relative to GJIC activity and investigated the potential mechanisms of action. In SVOG cells, treatment with BMP15 but not GDF9 significantly decreased Cx43 mRNA ...
Growth differentiation factor-15 (GDF-15) is a member of the TGF-β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal GDF15 transcript levels (r=0.54, P=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In ...
Aims: Growth differentiation factor 15 (GDF15) is induced during heart failure development, and may influence different processes in cardiac remodeling. While its anti-apoptotic action under conditions of ischemia-reperfusion have been shown, it remained unclear if this is a broadly protective effect applicable to other apoptotic stimuli. Furthermore, effects on cardiac hypertrophy remained obscure. Therefore, in the present study we investigated the effects of GDF15 on induction of hypertrophy and apoptosis in ventricular cardiomyocytes.. Methods and Results: Dose-response analysis of SMAD-binding affinity under stimulation with GDF15 revealed a maximal activation of SMADs, as the classical transcription factors in GDF15 signaling, by addition of 3 ng/ml GDF15 to cardiomyocytes. Under these conditions enhancement of SMAD1,5,8 phosphorylation, as another parameter of SMAD activation, was seen. At the same concentration, GDF15 enhanced hypertrophic growth as determined by an increase in cell size ...
Experimental observations that GDF-15 is produced by inflammatory cells involved in the pathogenesis of atherosclerosis led to the hypothesis that this cytokine may be useful in risk stratification of patients with cardiovascular disease.2,6 Subsequent studies3,21,22 demonstrated upregulated GDF-15 expression in cultured rat cardiomyocytes subjected to inflammatory cytokines, oxidative or nitrosative stress, simulated ischemia-reperfusion, or mechanical stretch. Mouse models showed a prolonged increase of GDF-15 expression in the myocardium in response to ischemia and reperfusion or long-term pressure overload.3,23 Retrospective data from the Womens Health Study showed that healthy women with GDF-15 concentrations greater than the 90th percentile (,856 ng/L) had a 2.7-fold higher risk of cardiovascular death, stroke, or MI.6 More recently, it was shown that GDF-15 on presentation in patients with NSTE ACS is an independent predictor of mortality and recurrent MI at 2 years10 and that patients ...
JACC Heart Fail. 2017 Oct;5(10):724-734. doi: 10.1016/j.jchf.2017.07.013. Sharma A, Stevens SR, Lucas J, Fiuzat M, Adams KF, Whellan DJ ...
J:60755 Rankin CT, Bunton T, Lawler AM, Lee SJ, Regulation of left-right patterning in mice by growth/differentiation factor-1. Nat Genet. 2000 Mar;24(3):262-5 ...
Background: Growth differentiation factor (GDF)-15, a stress responsive cytokine, is associated with the risk of CV events after an acute coronary syndrome (ACS). Unlike other established cardiac biomarkers, the level of GDF-15 remains elevated in sub-acute phase after ACS and gradually decreases over time. We evaluated the prognostic utility of GDF-15 in patients after ACS accounting for established markers and risk predictors.. Methods: GDF-15 (R&D Systems) and other established cardiac biomarkers (BNP, hsCRP and hsTnI) were measured at baseline in a randomly selected cohort of 4,968 patients enrolled within 30 days of hospitalization with ACS (median=14d) in SOLID-TIMI 52. Previously defined cutpoints were applied for GDF-15 concentration: ,1200 (n=3451), 1200-1800 (n=919), and , 1800 ng/L (n=598). Analyses were adjusted for established risk predictors, days from the ACS event and other markers. MACE was defined as CV death, MI or stroke. Median follow-up was 2.5 years.. Results: Patients ...
Complete data from 428 patients and all variables from the simple model were included in the multiple model. NT-proBNP, creatinine, uric acid, and GDF-15 were not normally distributed and were therefore transformed to their natural logarithms. HRs refer to an increase of 1 U in the Ln scale in these variables.. CI = confidence interval; Hb = hemoglobin; HR = hazard ratio; Ln = natural logarithm; other abbreviations as in Table 1.. ...
Background Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases. We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether ... read more plasma GDF-15 was associated with carotid plaque characteristics. Methods Circulating GDF-15 levels were determined by Luminex assay in a cohort of 1056 patients from the Athero-Express biobank. Composite endpoint was defined as major CVE, death and peripheral vascular interventions. Findings were validated in 473 patients from the independent Carotid Plaque Imaging Project biobank. Results GDF-15 levels did not associate with secondary CVE in the total cohort. However, following a significant interaction with sex, it was found to be strongly, independently predictive of secondary CVE in women but not men (quartile 4 ...
Mice harboring the hCD2-iCre transgene have the human CD2 promoter and locus control region (LCR) directing expression of an optimized variant of Cre recombinase (iCre) to T cells and B cells (all B cell and T cell progenitors) and mice may be useful for generating conditional mutations in T cells and B cells. Because of the integration site of the transgene, the hCD2-iCre transgene is linked to the agouti coat color genes.
...   In biology, folliculogenesis is the maturation of the ovarian follicle, a densely-packed shell of somatic cells that contains an
Growth differentiation factor 15 (GDF15) is a secreted protein with pleotropic functions from the transforming growth factor β (TGF-β) family. GDF15 is synthesized as a precursor and undergoes proteolytic cleavage to generate mature GDF15. The strong appetite-suppressing effect of mature GDF15 makes it an attractive therapeutic agent/target for diseases such as obesity and cachexia. In addition, clinical studies indicate that circulating, mature GDF15 is an independent biomarker for heart failure. We recently found that GDF15 functions as a heart-derived hormone that inhibits liver growth hormone signaling and postnatal body growth in the pediatric period. However, little is known about the mechanism of GDF15 maturation, in particular the enzymes that mediate GDF15 precursor cleavage. We investigated which candidate proteases can cleave GDF15 precursor and generate mature GDF15 in cardiomyocytes in vitro and mouse hearts in vivo. We discovered that three members of the proprotein convertase, ...
Background- An invasive treatment strategy improves outcomein patients with non-ST-elevation acute coronary syndromeat moderate to high risk. We hypothesized that the circulatinglevel of growth differentiation factor 15 (GDF-15) may improverisk stratification.. Methods and Results- The Fast Revascularization duringInStability in Coronary artery disease II (FRISC-II) trial randomizedpatients with non-ST-elevation acute coronary syndrometo an invasive or conservative strategy with a follow-up for2 years. GDF-15 and other biomarkers were determined on admissionin 2079 patients. GDF-15 was moderately elevated (between 1200and 1800 ng/L) in 770 patients (37.0%), and highly elevated(,1800 ng/L) in 493 patients (23.7%). Elevated levels ofGDF-15 independently predicted the risk of the composite endpoint of death or recurrent myocardial infarction in the conservativegroup (P=0.016) but not in the invasive group. A significantinteraction existed between the GDF-15 level on admission andthe effect of ...
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...
Materials. Neonatal Wistar rats were obtained from untimed pregnant females (Simonsen Labs, Gilroy, CA). The animal studies were conducted in accordance with the Policies on the Use of Animals and Humans in Neuroscience Research (1995), and animal protocols were approved by the local animal care committee. A total of 47 rat pups were used. 125I-Na was from PerkinElmer Life Sciences (Boston, MA). GDNF and CT-1 were purchased from Peprotech (Rocky Hill, NJ), tetanus toxin C-fragment (TTC) was from Calbiochem (La Jolla, CA), BDNF was a kind gift from Regeneron (Tarrytown, NY), and growth/differentiation factor-15 (GDF-15) was kindly provided by Jens Strelau and Klaus Unsicker (University of Heidelberg, Heidelberg, Germany). All electron microscopy (EM) tissue processing reagents were from EM Sciences (Gibbstown, NJ) except for lead citrate (Sigma, St. Louis, MO). DiI was from Molecular Probes (Eugene, OR). Autoradiographic developer (D19) and fixative (rapid fix) were from Kodak (Rochester, ...
Methods and Results-In 86 stable patients with HF and EF ≥45% in the Karolinska Rennes (KaRen) biomarker substudy, biomarkers were quantified by a multiplex immunoassay. Orthogonal projection to latent structures by partial least square analysis was performed on 87 biomarkers and 240 clinical variables, ranking biomarkers associated with New York Heart Association (NYHA) Functional class and the composite outcome (all-cause mortality and HF hospitalization). Biomarkers significantly correlated with outcome were analyzed by multivariable Cox regression and correlations with echocardiographic measurements performed. The orthogonal partial least square outcome-predicting biomarker pattern was run against the Ingenuity Pathway Analysis (IPA) database, containing annotated data from the public domain. The orthogonal partial least square analyses identified 32 biomarkers correlated with NYHA class and 28 predicting outcomes. Among outcome-predicting biomarkers, growth/differentiation factor-15 was ...
Results There were 44 patients with CTD-ILD, 28 patients without ILD and 31 healthy controls. The age and gender distributions of participants in all three groups were not different. Serum TGF-β and GDF-15 levels in patients with CTD-ILD and CTD without ILD were significantly higher than healthy controls (respectively, 3.05±0.26, 3.05±0.22, 1.39±0.33 pg/ml, p,0.001 for TGF-β and 1.17±0.17, 1.12±0.05, 0.95±0.21 pg/ml, p,0.001 for GDF-15). There were no statistically different from patients with ILD and without ILD for both TGF-β (p:0.864) and GDF-15 levels (p:0.146) in CTD. Also, GDF-15 and TGF-β levels of patients with systemic sclerosis were not different from other CTDs. ...
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GDF15 antibody (growth differentiation factor 15) for IHC-P, WB. Anti-GDF15 pAb (GTX54079) is tested in Human samples. 100% Ab-Assurance.
GDF10 antibody [N3C3] (growth differentiation factor 10) for ICC/IF, WB. Anti-GDF10 pAb (GTX118039) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
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Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development. Several members of this subfamily have been described, and named GDF1 through GDF15. GDF1 is expressed chiefly in the nervous system and functions in left-right patterning and mesoderm induction during embryonic development. GDF2 (also known as BMP9) induces and maintains the response embryonic basal forebrain cholinergic neurons (BFCN) have to a neurotransmitter called acetylcholine, and regulates iron metabolism by increasing levels of a protein called hepcidin. GDF3 is also known as "Vg-related gene 2" (Vgr-2). Expression of GDF3 occurs in ossifying bone during embryonic development and in the thymus, spleen, bone marrow brain, and adipose tissue of adults. It has a dual nature of function; it both inhibits and induces early stages of development in embryos. GDF5 is expressed in the developing central nervous system, ...
Myostatin, human recombinant protein, GDF-8, MSTN, Growth Differentiation Factor 8, MSTN Muscle Hypertrophy validated in (PBV10333r-10), Abcepta
Inflammatory cell recruitment to injured tissues is needed for repair, but an excessive inflammatory response can exacerbate injury. Tibor Kempf et al. now identify the cytokine GDF-15 as a new anti-inflammatory factor that dampens leukocyte recruitment in the setting of myocardial infarction in mice, thereby preventing cardiac rupture. GDF-15 blocks leukocyte extravasation from the blood into injured tissue by inhibiting the activation of cell surface integrin receptors. Inflammatory cell recruitment after myocardial infarction needs to be tightly controlled to permit infarct healing while avoiding fatal complications such as cardiac rupture. Growth differentiation factor-15 (GDF-15), a transforming growth factor-β (TGF-β)-related cytokine, is induced in the infarcted heart of mice and humans. We show that coronary artery ligation in Gdf15-deficient mice led to enhanced recruitment of polymorphonuclear leukocytes (PMNs) into the infarcted myocardium and an increased incidence of cardiac rupture.
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Results The levels of plasma GDF11 in the COPD group were decreased compared with the control groups in the two independent cohorts. The levels of plasma GDF11 were significantly positively correlated with pulmonary function data. The mRNA expression of GDF11 in mesenchymal cells from the COPD group was decreased. Chronic exposure to CSE decreased the production of GDF11. Treatment with GDF11 significantly inhibited CSE-induced cellular senescence and upregulation of inflammatory mediators, partly through Smad2/3 signalling in vitro. Daily GDF11 treatment attenuated cellular senescence and airspace enlargement in an elastase-induced mouse model of emphysema. ...
The objective of the present study was to examine the effects of neonatal exposure to either agonists or antagonists of androgen and estrogen receptors on the expression of growth and differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) and their cognate receptors (TGFBR1, BMPR1B, and BMPR2) in ovarian follicles of adult pigs. Piglets were injected subcutaneously with testosterone propionate (TP, an androgen, at 20 mg/kg bw), flutamide (FLU, an antiandrogen, at 50 mg/kg bw), 4-tert-octylphenol (OP, an estrogenic compound, 100 mg/kg bw), ICI 182,780 (ICI, an antiestrogen, 400 μg/kg bw), or corn oil (control) between postnatal Days 1 and 10 (n = 5/group). Ovarian follicles were excised from adult pigs on Days 8-11 of the estrous cycle. The expression of GDF9, BMP15, TGFBR1, BMPR1B and BMPR2 were examined in the population of preantral and small antral ovarian follicles using real-time PCR, Western blot and immunohistochemistry. In preantral follicles, the upregulation of GDF9 mRNA
Complete information for GDF11 gene (Protein Coding), Growth Differentiation Factor 11, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Next-day shipping cDNA ORF clones derived from NODAL nodal growth differentiation factor available at GenScript, starting from $99.00.
Objective-The assembly of a functional vascular system requires a coordinated and dynamic transition from activation to maturation. High vascular endothelial growth factor activity promotes activation, including junction destabilization and cell motility. Maturation involves junctional stabilization and formation of a functional endothelial barrier. The identity and mechanism of action of prostabilization signals are still mostly unknown. Bone morphogenetic protein receptors and their ligands have important functions during embryonic vessel assembly and maturation. Previous work has suggested a role for growth differentiation factor 6 (GDF6; bone morphogenetic protein 13) in vascular integrity although GDF6s mechanism of action was not clear. Therefore, we sought to further explore the requirement for GDF6 in vascular stabilization. ...
Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2-6 mm healthy follicles of mature porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml testosterone, 0-10 ng/ml SCF, 1 ng/ml FSH (granulosa), 0.01 ng/ml LH (theca) or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture) and with/without oocyte conditioned medium (OCM) or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids.Oocyte secreted factors were ...
Daniel A. Dumesic, M.D., JoAnne S. Richards, Ph.D.. Volume 100, Issue 1, Pages 23-38, July 2013. Abstract:. Activation of primordial follicles into the growing pool, selection of the dominant follicle and its eventual ovulation require complex endocrine and metabolic interactions, as well as intraovarian paracrine signals to coordinate granulosa cell proliferation, theca cell differentiation and oocyte maturation. Early preantral follicle development relies mostly upon mesenchymal-epithelial cell interactions, intraovarian paracrine signals and oocyte-secreted factors, while development of the antral follicle depends upon circulating gonadotropins as well as locally-derived regulators. In women with polycystic ovary syndrome (PCOS), ovarian hyperandrogenism, hyperinsulinemia from insulin resistance and altered intrafollicular paracrine signaling perturb activation, survival, growth and selection of follicles, causing accumulation of small antral follicles within the periphery of the ovary, ...
Certain microRNAs (miRs) have important roles in the maintenance of bone development and metabolism, and a variety of miRs are known to be deregulated in diabetes. The present study investigated the role of miR‑203‑3p in the regulation of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The results indicated that miR‑203‑3p inhibited osteogenesis in the jaws of diabetic rats and in rat bone marrow mesenchymal stem cells cultured in high‑glucose medium. A luciferase re-porter assay was used to verify the bioinformatics prediction that miR‑203‑3p targets the 3‑untranslated region of Smad1, which is an important mediator of the bone morphogenetic protein (BMP)/Smad pathway ...
The fact that a mutation in Alk5 had an effect in the Acvr2b‐null background indicates that Alk5 must also be coupling to another type II receptor, most probably Acvr2, to mediate the effects of GDF11 on embryonic development. In support of this idea, mutations in Acvr2 have been shown to augment the phenotypes observed in Acvr2b−/− animals (Oh et al, 2002). Unlike Acvr2b−/− mutants, however, Acvr2−/− animals lack any vertebral patterning defects, indicating that although the Acvr2b−/− strain is genetically sensitized for those phenotypes, the Acvr2−/− strain is not. Together with the absence of effects of ALK4 and ALK7 in axial patterning, the lack of ALK4 and ALK7 expression in relevant patterning structures and the fact that GDF11, similar to TGF‐β, signals through Smad2 and Smad3, our results strongly indicate that GDF11 uses the TGF‐β receptor ALK5 in vivo to control several developmental events. Our study has not addressed the possible participation of other ...
As it is known that the normal tumor microenvironment becomes corrupted during tumor development, which is reflected by appearance of a large and heterogeneous category of cancer-associated fibroblasts (CAFs) [28]. CAF cells are considered active modulators of the tumor microenvironment among many solid tumors [29-31]. However, few studies have directly addressed the role of the CAFs in the BM of leukemia. In the present study, we demonstrate that functional CAFs are widespread in the BM of AML patients and could serve as a critical chemo-protective element for AML cells by producing an abundance of GDF15.. As we all know, AML cells interact both anatomically and functionally with the stroma within the BM microenvironment. These interactions have a critical role in the development, progression and relapse of AML. A recent study has suggested discoidin domain receptor 1 (DDR1), a class of collagen-activated receptor tyrosine kinase (RTK) was highly upregulated on bone marrow (BM)-derived CD33+ ...
21] The board observes that such a dichotomy arose between, on the one hand, the disclosure in the patent application underlying decision T 1329/04 (lack of the seven cystein residues with their peculiar spacing required for a protein (in that case, GDF-9) to belong to the TGF-beta superfamily - see T 1329/04 [7] - and the lack of functional characterisation of GDF-9 - see ibidem, [9]) and, on the other hand, the teaching in post-published document D4 that GDF-9 was indeed a growth differentiation factor (see T 1329/04 [12]). Hence, the then competent board concluded that there was not enough evidence in the application as filed to make it at least plausible that a solution had been found to the problem alleged to be solved ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
CPB653Po21, OVA Conjugated Myostatin (MSTN), 肌肉生长抑制素(MSTN)卵白蛋白偶联物, GDF8; Growth Differentiation Factor 8 | 仅供体外研究使用,不用于临床诊断!请索取进口关税税单及报关单!
Chung H.K., Ryu D., Kim K.S., Chang J.Y., Kim Y.K., Yi H.-S., Kang S.G., Choi M.J., Lee S.E., Jung S.B., Ryu M.J., Kim S.J., Kweon G.R., Kim H., Hwang J.H., Lee C.-H., Lee S.-J., Wall C.E., Downes M., Evans R.M., Auwerx J., Shong M. (2017) Growth differentiation factor 15 (GDF15) is a myomitokine governing systemic energy homeostasis. J Cell Biol. 216: 149-165. doi: 10.1083/jcb.201607110.. ...
A schematic diagram showing folliculogenesis and oogenesis. The former involves the maturation of a follicle within the ovary while the latter involves the release of the ovum/egg from it, - Stock Image F002/0936
زمینه مطالعاتی: انتخاب به وسیله ژنتیک مولکولی روی ژن-های منحصر بفرد یک روش مطمئن برای بهبود ژنتیکی صفات مهم اقتصادی در حیوانات اهلی می-باشد. صفت چندقلوزایی یکی از صفات مهم اقتصادی در صنعت گوسفندداری می-باشد که در سال-های اخیر توجه متخصصین اصلاح نژاد را به خود جلب کرده است. ژن فاکتور رشد و تمایز شماره 9 (GDF9) از مهم-ترین ژن-های کاندیدای موثر بر صفت چندقلوزایی در گوسفند می-باشد. هدف: این آزمایش جهت بررسی وجود چند شکلی در جایگاه نیمه دوم (منتهی به3) اگزون 2 ژن GDF9 گوسفند نژاد کرمانی انجام شد. روش کار: در این مطالعه، از 102 رأس گوسفند خونگیری شد. پس از استخراج DNA، تعیین
Rationale: GDF11 (Growth Differentiation Factor 11) is a member of the TGFβ super family of secreted factors, which play an important role in the regulation of cell processes including proliferation, differentiation, death, adhesion, and migration. Recently it was shown that circulating GDF11 levels fall with aging and this change is associated with pathological cardiac hypertrophy (PCH). Restoring GDF11 to normal levels was shown to rescue PCH.. Objective: To determine if we can confirm the hypothesis that correcting the levels of a single factor, GDF11, determines aging related PCH.. Methods and Results: We used the study design described by Loffredo et al, 2013. Investigators were blinded to treatment group. 24 month old C57BL/6 male mice were given a daily injection of recombinant GDF11 at 0 .1mg/kg or vehicle for 28 days. GDF11 bioactivity was confirmed in-vitro. After treatment, GDF11 levels were significantly increased but there was no difference in heart weight (HW) to body weight (BW) ...
Yangs laboratory has been studying myostatin, a protein playing a dominant role in reducing muscle mass. By genetically blocking the function of myostatin by its partial DNA sequences, mice were developed with 40 percent more muscle mass. Yangs graduate student Zicong Li, the first author of the publication, hypothesized that this gene suppression strategy would also work to stimulate skeletal development by inhibiting growth differentiation factor 11 (GDF11), a similar protein to myostatin, and produce live animals. Previously, the mice with complete removal of the GDF11 gene or knockout mice died shortly after birth. In collaboration with Dr. Stefan Moisyadis laboratory in the UH Institute of Biogenesis Research, they generated the transgenic mice by using a new single plasmid system of piggyBac transgene delivery, which offers greater transposition rates and precision ...
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2000). "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/ ... Vitt U, Mazerbourg S, Klein C, Hsueh A (2002). "Bone morphogenetic protein receptor type II is a receptor for growth ... Vitt UA, Mazerbourg S, Klein C, Hsueh AJ (2003). "Bone morphogenetic protein receptor type II is a receptor for growth ... The cell surface receptor through which GDF9 generates a signal is the bone morphogenetic protein type II receptor (BMPR2). ...
... bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions". Proceedings of the National Academy of ... ROS also interacts with ERK pathway that leads to activation of Ras, MEK and MEK-like proteins. These proteins activate protein ... Bone morphogenetic proteins/ Mothers against decapentaplegic/ Inhibitor of differentiation), mediated by transcription factors ... In TGF-β (Transforming Growth Factor β) pathway, BMP (Bone Morphogenic Protein), Activin and Nodal ligands bind to their ...
It acts as a regulator of TGFβ family (such as bone morphogenetic proteins) activity by competing with SMAD4 and preventing the ... Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (2001). "Promoting bone morphogenetic protein signaling through ... The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein ... SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene. SMAD6 is a protein that, ...
The BMPs bind to the bone morphogenetic protein receptor type-2 (BMPR2). They are involved in a multitude of cellular functions ... Bone morphogenetic proteins cause the transcription of mRNAs involved in osteogenesis, neurogenesis, and ventral mesoderm ... The TGF beta superfamily of ligands include: Bone morphogenetic proteins (BMPs), Growth and differentiation factors (GDFs), ... "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132-42. doi: ...
By occupying type I receptors for Activin and bone morphogenetic protein (BMP), it also plays a role in negative feedback of ... Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling ... "Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B ... Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene. SMAD7 is a protein ...
Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic ... BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15 ... However, BMPR2 can't bind BMP15 and GDF9 without the assistance of bone morphogenetic protein receptor 1B (BMPR1B) and ... "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine ...
Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling ... STAM-binding protein is a protein that in humans is encoded by the STAMBP gene. Cytokine-mediated signal transduction in the ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038/ ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038/ ...
Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling ... "Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming ... potency of cell proliferation and differentiation responses to transforming growth factor beta and bone morphogenetic protein ... Thus, the two proteins could be caught in a "vicious cycle" of regulation. Pin1 causes both itself and Smad2 to be associated ...
The BMPs bind to the bone morphogenetic protein receptor type II (BMPR2). Some of the proteins of the BMP family are BMP4 and ... Then active Smoothened protein is able to inhibit PKA and Slimb, so that the Ci protein is not cleaved. This intact Ci protein ... The binding of Wnt to a Frizzled protein activates the Dishevelled protein. In its active state the Dishevelled protein ... "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". The EMBO Journal. 20 (15): ...
"A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs)". BMC ... Smad nuclear-interacting protein 1 is a protein that in humans is encoded by the SNIP1 gene. SNIP1 has been shown to interact ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-1178. doi:10.1038/ ... Roche KC, Wiechens N, Owen-Hughes T, Perkins ND (2004). "The FHA domain protein SNIP1 is a regulator of the cell cycle and ...
"A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs)". BMC ... The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key ... "A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs)". BMC ... "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". ...
... is a protein that in humans is encoded by the BMP15 gene. It's mainly involved in ... "Entrez Gene: BMP15 bone morphogenetic protein 15". Persani, L.; Rossetti, R.; Di Pasquale, E.; Cacciatore, C.; Fabre, S. (2014 ... 2001). "Bone morphogenetic protein-15. Identification of target cells and biological functions". J. Biol. Chem. 275 (50): 39523 ... Moore RK, Otsuka F, Shimasaki S (2003). "Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells". J. ...
... or BMP7 (also known as osteogenic protein-1 or OP-1) is a protein that in humans is encoded by the ... The protein encoded by this gene is a member of the TGF-β superfamily. Like other members of the bone morphogenetic protein ... Reddi AH (2000). "Bone morphogenetic proteins and skeletal development: the kidney-bone connection". Pediatr. Nephrol. 14 (7): ... bone morphogenetic protein 7 (BMP-7) versus autologous bone grafting for tibial fractures]". Unfallchirurg (in German). 110 (11 ...
... , also known as BMP1, is a protein which in humans is encoded by the BMP1 gene. There are seven ... Although other bone morphogenetic proteins are members of the TGF-beta superfamily, BMP1 encodes a protein that is not closely ... 1993). "Mapping of the bone morphogenetic protein 1 gene (BMP1) to 8p21: removal of BMP1 from candidacy for the bone disorder ... BMP1 belongs to the peptidase M12A family of bone morphogenetic proteins (BMPs). It induces bone and cartilage development. ...
"Entrez Gene: BMP4 bone morphogenetic protein 4". Miyazono K, Kamiya Y, Morikawa M (January 2010). "Bone morphogenetic protein ... type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein ... Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23 BMP4 is ... It, like other bone morphogenetic proteins, is involved in bone and cartilage development, specifically tooth and limb ...
1998). "Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis". J. Bone Miner ... GDF6 interacts with bone morphogenetic proteins (BMPs) to form heterodimers that may work to regulate neural induction and ... Reddi AH (1995). "Cartilage morphogenesis: role of bone and cartilage morphogenetic proteins, homeobox genes and extracellular ... 2005). "Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ...
骨塑型蛋白受體 1B(英语:Bone morphogenetic protein receptor 1B). 卵巢功能障礙、高促性腺激素性性腺功能低下症(英语:Hypergonadotropic hypogonadism)、肢端肢中部骨骺軟骨發育不良( ... Bone morphogenetic protein 15). 高促性腺激素性卵巢衰竭(POF4) ... FOX蛋白L2(英语:Forkhead Box Protein L2). 和第一型先天性家族性
Dpp is the Drosophila homolog of the vertebrate bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily ... It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs ... In Drosophila, the receptor for Dpp is formed by two proteins, Thickveins (Tkv) and Punt. Like Dpp itself, Tkv and Punt are ... When a cell receives a Dpp signal, the receptors are able to activate an intracellular protein called mothers against dpp (mad ...
... a bone morphogenetic protein. Matrix 1992; 12:369-80. Ripamonti U, Heliotis M, van den Heever B, Reddi AH. Bone morphogenetic ... isolation and purification of bone morphogenetic proteins (BMPs) that are involved in bone formation and repair. The molecular ... Osteogenin (bone morphogenetic protein-3) stimulates cartilage formation by chick limb bud cells in vitro. Dev Biol 1991; 146: ... Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth ...
... and bone morphogenetic proteins. Evidence suggests that bone cells produce growth factors for extracellular storage in the bone ... Most of the bones of the skull are flat bones, as is the sternum. Sesamoid bones are bones embedded in tendons. Since they act ... Bone tissue is a mineralized tissue of two types, cortical bone and cancellous bone. Other types of tissue found in bones ... Artificial bone Bone health Distraction osteogenesis National Bone Health Campaign Cells in bone marrow Scanning electron ...
Shim S, Bae N, Han JK (July 2002). "Bone morphogenetic protein-4-induced activation of Xretpos is mediated by Smads and Olf-1/ ... Zinc finger protein 423 is a protein that in humans is encoded by the ZNF423 gene. The protein encoded by this gene is a ... "ZFP423 coordinates Notch and bone morphogenetic protein signaling, selectively up-regulating Hes5 gene expression". The Journal ... OAZ protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ...
... of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced ... The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein ... protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces ... "Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins". Nucleic Acids Res. 29 (3): 732-42. doi: ...
... bone morphogenetic protein-7) to initiate rapid bone formation". J Bone Miner Res. 12: 1584-95. doi:10.1359/jbmr.1997.12. ... bone morphogenetic protein-7) to initiate rapid bone formation. (October 1997) Transforming growth factor-beta 1: induction of ... induction of bone morphogenetic protein genes expression during endochondral bone formation in the baboon, and synergistic ... "Enhanced activity of demineralised bone matrix augmented with xenogeneic bone morphogenetic protein complex in rats". SADJ. 67 ...
In 2006, while examining the available literature on bone morphogenetic protein 2 (BMP-2), used to stimulate bone growth in ... he gained public prominence in 2011 for his research that uncovered the harmful side effects of bone morphogenetic protein 2 ... Tomislav Smoljanović (born 15 July 1977) is a Croatian medical scientist, physician, and a retired rower. Smoljanović won ...
"Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell Sci. 112 (20): 3519 ... "Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent ... Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene. ACVR2A is an activin type 2 receptor. This ... Barbara NP, Wrana JL, Letarte M (1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of ...
This linkage is further evidenced by the fact that two of the genes, HAO1 and BMP2, affecting medullary bone (the part of the ... The HBB gene encodes information to make the beta-globin subunit of hemoglobin, which is the protein red blood cells use to ... Foods with high levels of protein must be avoided. These include breast milk, eggs, chicken, beef, pork, fish, nuts, and other ... Both males and females with larger combs have higher bone density and strength, which allows females to deposit more calcium ...
Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial HypertensionCLINICAL PERSPECTIVE. A View on the Right ... Bone morphogenetic protein receptor type 2 mutations, clinical phenotypes and outcomes of Japanese patients with sporadic or ... Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred ... Background-The effect of a mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene on right ventricular (RV) ...
Cloning and characterization of a human type II receptor for bone morphogenetic proteins. Proc Natl Acad Sci U S A. 1995; 92: ... Background- Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming ... Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. ... Recently, heterozygous germline mutations that involve the gene encoding the type II bone morphogenetic protein receptor (BMPR2 ...
T1 - The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult ... The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult ... The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult ... The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult ...
Bone morphogenetic protein 15 is a protein that in humans is encoded by the BMP15 gene. Its mainly involved in ... "Entrez Gene: BMP15 bone morphogenetic protein 15". Persani, L.; Rossetti, R.; Di Pasquale, E.; Cacciatore, C.; Fabre, S. (2014 ... 2001). "Bone morphogenetic protein-15. Identification of target cells and biological functions". J. Biol. Chem. 275 (50): 39523 ... Moore RK, Otsuka F, Shimasaki S (2003). "Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells". J. ...
The goal of this study is to analyze a partial sequence of bone morphogenetic protein 4 (Bmp4), a gene known to be involved in ...
Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor... ... Quantitative analysis of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) gene expression in ... Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) play critical roles in folliculogenesis, ... Otsuka F, Yao Z, Lee TH, Yamamoto S, Erickson GF, Shimasaki S: Bone morphogenetic protein-15. J Biol Chem. 2000, 275: 39523- ...
Fluorescent Proteins, RNAi, Viral Packaging and Protein expression. ... to be involved in oocyte maturation and follicular development as a homodimer or by forming heterodimers with a related protein ...
Variation in bone morphogenetic protein 15 is not associated with spontaneous human dizygotic twinning. Zhao, Zhen Zhen, ... Variation in bone morphogenetic protein 15 is not associated with spontaneous human dizygotic twinning ... In sheep, heterozygous loss of function mutations in bone morphogenetic protein 15 (BMP15) increase ovulation and hence ... In sheep, heterozygous loss of function mutations in bone morphogenetic protein 15 (BMP15) increase ovulation and hence ...
Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Biol Reprod 67:473-480. ... Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem 278:304-310. ... Bone morphogenetic protein-15 identification of target cells and biological functions. J Biol Chem 275:39523-39528. ... Role of Bone Morphogenetic Proteins-6 and -7 (BMP-6 and -7) in the regulation of early foliculogenesis in mammals. Rev Bras ...
Wu YT, Tang L, Cai J, Lu XE, Xu J, Zhu XM, Luo Q, Huang HF: High bone morphogenetic protein-15 level in follicular fluid is ... Wu YT, Wang TT, Chen XJ, Zhu XM, Dong MY, Sheng JZ, Xu CM, Huang HF: Bone morphogenetic protein-15 in follicle fluid combined ... Follicular fluid samples from both groups were collected for bone morphogenetic protein-15 (BMP-15) and growth differentiation ... Dehydroepiandrosterone improves follicular fluid bone morphogenetic protein-15 and accumulated embryo score of infertility ...
Bone Morphogenetic Protein 15 Knockdown Inhibits Porcine Ovarian Follicular Development and Ovulation. ... Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice. ... Inhibition of Casein Kinase II by CX-4945, But Not Yes-associated protein (YAP) by Verteporfin, Enhances the Antitumor Efficacy ... 15.. Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in ...
Description bone morphogenetic protein 15 Also known as GDF9B, ODG2, POF4 Species Homo sapiens ...
Bone morphogenetic protein 15 may promote follicle selection in the hen. Gen Comp Endocrinol (2016) 235:170-6. doi:10.1016/j. ... Protein-Protein Interaction (PPI) Networks. Protein-protein interaction networks were constructed based on the information from ... Bone morphogenetic protein 4 supports the initial differentiation of hen (Gallus gallus) granulosa cells. Biol Reprod (2013) 88 ... Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen ...
Invitrogen Anti-BMP-15 Polyclonal, Catalog # PA5-95615. Tested in Western Blot (WB) and Immunohistochemistry (Paraffin) (IHC (P ... BMP15, or GDF9B is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta ... Bone morphogenetic protein 15; GDF-9B; GDF9B; growth differentiation factor-9B; Growth/differentiation factor 9B ... ovarian follicle development female gamete generation positive regulation of pathway-restricted SMAD protein phosphorylation ...
Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol. ... Gazzerro E, Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord. 2006;7(1-2):51-65.. View ... We emphasize the roles of bone morphogenetic proteins (BMPs), activins, and SMADs, WNT signaling, and recently uncovered ... Langenfeld EM, Kong Y, Langenfeld J. Bone morphogenetic protein-2-induced transformation involves the activation of mammalian ...
Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc ... and bone morphogenetic protein 15 (BMP15) from the oocyte, which engage a receptor system on the surrounding granulosa cells (8 ... For example, the Drosophila diaphanous (dia) gene is involved in cytokinesis and other morphogenetic processes that are ... NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in ...
Fluorescent Proteins, RNAi, Viral Packaging and Protein expression. ... 100 µg) BMP3 was originally purified from bone as osteogenin, which induces osteogenic differentiation. However, recombinant ...
Fluorescent Proteins, RNAi, Viral Packaging and Protein expression. ...
Fluorescent Proteins, RNAi, Viral Packaging and Protein expression. ...
Fluorescent Proteins, RNAi, Viral Packaging and Protein expression. ... 100 µg) BMP2K is a putative serine/threonine protein kinase which is elevated under BMP-2-induced differentiation. ...
Fluorescent Proteins, RNAi, Viral Packaging and Protein expression. ...
Protein related to DAN and cerberus is a bone morphogenetic protein antagonist that participates in ovarian paracrine ... Vitt, U. A., Mazerbourg, S., Klein, C. and Hsueh, A. J. (2002). Bone morphogenetic protein receptor type II is a receptor for ... Dudley, A. T., Lyons, K. M. and Robertson, E. J. (1995). A requirement for bone morphogenetic protein-7 during development of ... Lee, W. S., Otsuka, F., Moore, R. K. and Shimasaki, S. (2001). Effect of bone morphogenetic protein-7 on folliculogenesis and ...
18006624 - Phosphorylation of bone morphogenetic protein-15 and growth and differentiation factor-.... 9491384 - The c-kit ... In the absence of ATP from cell extracts, protein kinase activity of Mos was lost within 6 h on ice even though the Mos protein ... HSP70 Heat-Shock Proteins / physiology*. Mice. Proto-Oncogene Proteins c-mos / physiology*. ... Next Document: Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals .... ...
Effects of immunization against bone morphogenetic protein-15 and growth differentiation factor-9 on ovarian function in mares. ... Expression of mRNA Encoding Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 during Follicular Formation and ... Evaluation of antibody response to an adjuvanted hapten-protein vaccine as a potential inhibitor of sexual maturation for ...
The protein encoded by this gene is a member of the bone morphogenetic protein family which is part of the transforming growth ... Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells.. Moore RK, Otsuka F, Shimasaki S.J Biol Chem. ... Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and ... It is thought that this protein may be involved in oocyte maturation and follicular development as a homodimer or by forming ...
  • Thus, cell survival was decreased, glial fibrillary acidic protein (GFAP) expression was reduced, whereas the number of oligodendrocytes increased. (elsevier.com)
  • Transferrin receptor-2 activation by its ligand holotransferrin led to extracellular signal regulated kinase (ERK)/mitogen activated protein kinase pathway stimulation and the ERK specific inhibitor U0-126 blunted holotransferrin-mediated induction of hepcidin. (haematologica.org)
  • Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. (jove.com)
  • The Kit proto-oncogene encodes a tyrosine kinase receptor whose ligand is a paracrine protein called stem cell factor (SCF), which is important in hematopoiesis (formation of cells in blood). (wikipedia.org)
  • Ligand proteins binding to the extracellular domain induce proteolytic cleavage and release of the intracellular domain, which enters the cell nucleus to modify gene expression. (wikipedia.org)
  • The signaling system involving this protein and its ligand, Sdf1, is necessary and sufficient to direct PGC migration in fish. (wikipedia.org)
  • All three pathways are activated by binding a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. (wikipedia.org)
  • Purified, E. coli-derived, recombinant human bone morphogenetic protein 8 (rhBMP-8) monomer. (neuromics.com)
  • Methods: Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). (whiterose.ac.uk)
  • PURPOSE: The aim of the present study was to test whether or not a synthetic matrix consisting of a polyethylene glycol (PEG) hydrogel containing recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with grafting materials enhances bone regeneration compared with grafting alone or empty control sites. (uzh.ch)
  • By expressing a recombinant form of the N-terminal domain I of the protein and demonstrating that digestion of the peptide with either heparanase or chondroitinase did not lead to complete loss of the peptide's activity, it was shown that chondroitin sulfate chains can be added to human perlecan. (wikipedia.org)
  • This was in agreement with previous data showing chondroitin sulfate GAG chains attached to bovine perlecan produced by chondrocytes and that recombinant human domain I protein was glycosylated with both heparan and chondroitin sulfate chains when expressed in Chinese Hamster Ovary cells. (wikipedia.org)
  • In order to allow for the growth of precursor neural tissues, as opposed to precursor bone or cartilage tissues, BMP expression is decreased in the neural plate, specifically along the medial line, where the neural groove will soon form. (wikipedia.org)
  • Once miR-155 pri-miRNA is transcribed, this transcript is cleaved by the nuclear microprocessor complex, of which the core components are the RNase III type endonuclease Drosha and the DiGeorge critical region 8 (DGCR8) protein, to produce a 65 nucleotide stem-loop precursor miRNA (pre-mir-155) (see Figure 2). (wikipedia.org)
  • This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex. (wikipedia.org)
  • The Mitochondrial-processing peptidase subunit alpha precursor protein is 58.2 KDa in size and composed of 525 amino acids. (wikipedia.org)
  • The precursor protein contains a 33 amino acid N-terminal fragment as mitochondrion targeting sequence. (wikipedia.org)
  • Containing the catalytic site, the beta subunit PMPCB protein cleaves presequences (transit peptides) from mitochondrial protein precursors and releases of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2. (wikipedia.org)
  • Many mitochondrial proteins are synthesized in a precursor form that contains mitochondria targeting sequence. (wikipedia.org)
  • Components that are essential for osteoblast bone formation include mesenchymal stem cells (osteoblast precursor) and blood vessels that supply oxygen and nutrients for bone formation. (wikipedia.org)
  • Based on our identification of c-Mos-Hsp70 interaction, one of the roles of ATP may be to assist the regulation of c-Mos via ATP involvement in the protein-folding function of Hsp70 and possibly other molecular chaperones. (biomedsearch.com)
  • Understanding which are the molecular regulators of BMP2 activity during bone repair and studying the BMP2 presentation via the bone extracellular matrix is therefore essential for a future new generation of BMP2-delivering biomaterials. (minatec.org)
  • Perlecan consists of a core protein of molecular weight 470 kDa to which three long chains (each approximately 70-100 kDa) of glycosaminoglycans (often heparan sulfate, HS but can be chondroitin sulfate, CS) are attached. (wikipedia.org)
  • The localization of gene expression and protein were ascertained by histochemistry. (springer.com)
  • Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression, 855-68. (usd.edu)
  • as a result of proteolysis, the intracellular domain is liberated and can enter the nucleus to engage other DNA-binding proteins and regulate gene expression. (wikipedia.org)
  • Collectively, these proteins redirect SWI/SNF to activate the cardiac program of gene expression. (wikipedia.org)
  • GDF11 gene expression and protein abundance decreases with age, and it shows differential abundance between young and old mice in parabiosis procedures, causing youthful regeneration of cardiomyocytes, a reduction in the brain natriuretic peptide (BNP) and in the atrial natriuretic peptide (ANP). (wikipedia.org)
  • Their main targets are protein kinases as PKA and PKG, being then involved in phosphorylation mediated responses. (wikipedia.org)
  • Regulation of protein activity mainly involves phosphorylation/dephosphorylation events, leading to its activation or inhibition. (wikipedia.org)
  • The linker region contains important regulatory peptide motifs including potential phosphorylation sites for mitogen-activated protein kinases(MAPKs), Erk-family MAP kinases, the Ca2+ /calmodulin-dependent protein kinase II (CamKII) and protein kinase C (PKC). (wikipedia.org)
  • Moreover, accumulating evidence now suggests that JNK is directly involved in the regulation of the cytoskeleton, particularly in maintaining the stability of microtubules by controlling the phosphorylation of microtubule-associated proteins (MAPs). (asm.org)
  • Scientists have identified a new and unusual protein that reduces, in laboratory mice, kidney damage caused by chronic renal disease and acute toxic injuries. (rxpgnews.com)
  • Mice that couldn't secrete KCP protein were more susceptible to renal injuries, had higher mortality rates and showed more fibrosis and scarring than normal mice. (rxpgnews.com)
  • To determine the effects of KCP in experimental animals, Dressler created a strain of knock-out mice that were unable to produce KCP protein, because they lacked the required gene. (rxpgnews.com)
  • Investigations of TGF-β signaling in preantral follicles of female mice reveal differential roles for bone morphogenetic protein 15. (semanticscholar.org)
  • ABD produced in mice with CKD in the absence of hyperparathyroidism was successfully reversed with a bone anabolic, BMP-7, associated with a reduction in plasma phosphorus. (asnjournals.org)
  • Elevated expression of bone morphogenetic protein 6 (BMP6) was recently reported in the epithelia of SS patients, and hypofunction and increased lymphocytic infiltration of the salivary gland were induced by the overexpression of BMP6 in normal mice [ 8 ]. (hindawi.com)
  • Experiments in mice have shown that noggin also plays a role in learning, cognition, bone development, and neural tube fusion. (wikipedia.org)
  • These two protein signaling molecules and their BMPR2 mediated effects play an important role in follicle development in preparation for ovulation. (wikipedia.org)