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.

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.

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-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.

A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.

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.

A bone morphogenetic protein that is a potent inducer of bone formation. It also functions as a regulator of MESODERM formation during EMBRYONIC DEVELOPMENT.

Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.

Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.

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.

A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.

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.

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.

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).

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.

The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.

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.

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.

A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment.

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.

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.

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.

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.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

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.

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.

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.

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.

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.

A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)

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.

The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.

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.

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.

Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.

A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS and regulates BONE MORPHOGENETIC PROTEIN signaling.

The process of bone formation. Histogenesis of bone including ossification.

A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.

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.

Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.

Renewal or repair of lost bone tissue. It excludes BONY CALLUS formed after BONE FRACTURES but not yet replaced by hard bone.

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.

A family of BONE MORPHOGENETIC PROTEIN-related proteins that are primarily involved in regulation of CELL DIFFERENTIATION.

SNARE proteins where the central amino acid residue of the SNARE motif is an ARGININE. They are classified separately from the Q-SNARE PROTEINS where the central amino acid residue of the SNARE motif is a GLUTAMINE. This subfamily contains the vesicle associated membrane proteins (VAMPs) based on similarity to the prototype for the R-SNAREs, VAMP2 (synaptobrevin 2).

A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.

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.

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.

A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.

A bone morphogenetic protein that plays an essential role in the regulation of ovarian folliculogenesis.

Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.

A synaptic membrane protein involved in MEMBRANE FUSION of SYNAPTIC VESICLES with the presynaptic membranes. It is the prototype member of the R-SNARE PROTEINS.

Bone loss due to osteoclastic activity.

Transport proteins that carry specific substances in the blood or across cell membranes.

A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES.

A growth differentiation factor that plays a role in the neural differentiation, specifically in the retinal development of the EYE.

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.

A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.

A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the N-terminal SNARE domain of SNAP-25 and which also are most similar to the N-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.

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.

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.

Tumors or cancer located in bone tissue or specific BONES.

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.

Diseases of BONES.

Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.

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.

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.

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.

The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.

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.

A family of proteins involved in intracellular membrane trafficking. They interact with SYNTAXINS and play important roles in vesicular docking and fusion during EXOCYTOSIS. Their name derives from the fact that they are related to Unc-18 protein, C elegans.

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.

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.

A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the C-terminal SNARE domain of SNAP-25 and which also are most similar to the C-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.