A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.
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.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
Glycoproteins found on the membrane or surface of cells.
Bone loss due to osteoclastic activity.
Dissolution of bone that particularly involves the removal or loss of calcium.
Transport proteins that carry specific substances in the blood or across cell membranes.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
Tumors or cancer located in bone tissue or specific BONES.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
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 membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
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.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
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.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.

Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase. (1/1553)

Receptor activator of NF-kappaB (RANK) is a recently cloned member of the tumor necrosis factor receptor (TNFR) superfamily, and its function has been implicated in osteoclast differentiation and dendritic cell survival. Many of the TNFR family receptors recruit various members of the TNF receptor-associated factor (TRAF) family for transduction of their signals to NF-kappaB and c-Jun N-terminal kinase. In this study, the involvement of TRAF family members and the activation of the JNK pathway in signal transduction by RANK were investigated. TRAF1, 2, 3, 5, and 6 were found to bind RANK in vitro. Association of RANK with each of these TRAF proteins was also detected in vivo. Expression of RANK in cultured cells also induced the activation of JNK, which was blocked by a dominant-negative form of JNK. Furthermore, by employing various C-terminal deletion mutants of RANK, the regions responsible for TRAF interaction and JNK activation were identified. TRAF5 was determined to bind to the C-terminal 11 amino acids and the other TRAF members to a region N-terminal to the TRAF5 binding site. The domain responsible for JNK activation was localized to the same region where TRAF1, 2, 3, and 6 bound, which suggests that these TRAF molecules might mediate the RANK-induced JNK activation.  (+info)

TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces cytokine production in dendritic cells. (2/1553)

TNF-related activation-induced cytokine (TRANCE) is a member of the TNF family recently identified in activated T cells. We report here that TRANCE mRNA is constitutively expressed in memory, but not naive, T cells and in single-positive thymocytes. Upon TCR/CD3 stimulation, TRANCE mRNA and surface protein expression are rapidly up-regulated in CD4+ and CD8+ T cells, which can be further enhanced on CD4+ T cells by CD28-mediated costimulation. However, TRANCE induction is significantly suppressed when cells are stimulated in the presence of IL-4, but is not modified in the presence of IFN-alpha, IFN-gamma, TGF-beta, TNF-alpha, or IL-2. High levels of TRANCE receptor expression are found on mature dendritic cells (DCs). In this study we show that activated T and B cells also express TRANCE receptor, but only at low levels. TRANCE, however, does not exert any significant effect on the proliferation, activation, or survival of those cells. In DCs, TRANCE induces the expression of proinflammatory cytokines (IL-6, IL-1) and T cell growth and differentiation factors (IL-12, IL-15) in addition to enhancing DC survival. Moreover, TRANCE cooperates with CD40 ligand or TNF-alpha to further increase the viability of DCs, suggesting that several TNF-related molecules on activated T cells may cooperatively regulate the function and survival of DCs to enhance T cell-mediated immune responses.  (+info)

Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif. (3/1553)

Various members of the tumor necrosis factor (TNF) receptor superfamily activate nuclear factor kappaB (NF-kappaB) and the c-Jun N-terminal kinase (JNK) pathways through their interaction with TNF receptor-associated factors (TRAFs) and NF-kappaB-inducing kinase (NIK). We have previously shown that the cytoplasmic domain of receptor activator of NF-kappaB (RANK) interacts with TRAF2, TRAF5, and TRAF6 and that its overexpression activates NF-kappaB and JNK pathways. Through a detailed mutational analysis of the cytoplasmic domain of RANK, we demonstrate that TRAF2 and TRAF5 bind to consensus TRAF binding motifs located in the C terminus at positions 565-568 and 606-611, respectively. In contrast, TRAF6 interacts with a novel motif located between residues 340 and 358 of RANK. Furthermore, transfection experiments with RANK and its deletion mutants in human embryonic 293 cells revealed that the TRAF6-binding region (340-358), but not the TRAF2 or TRAF5-binding region, is necessary and sufficient for RANK-induced NF-kappaB activation. Moreover, a kinase mutant of NIK (NIK-KM) inhibited RANK-induced NF-kappaB activation. However, RANK-mediated JNK activation required a distal portion (427-603) of RANK containing the TRAF2-binding domain. Thus, our results indicate that RANK interacts with various TRAFs through distinct motifs and activates NF-kappaB via a novel TRAF6 interaction motif, which then activates NIK, thus leading to NF-kappaB activation, whereas RANK most likely activates JNK through a TRAF2-interacting region in RANK.  (+info)

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. (4/1553)

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.  (+info)

TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation. (5/1553)

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4(+) T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4(+) T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4(+) T cell responses that produce normal levels of interferon gamma, suggesting a CD40L/CD40-independent mechanism of CD4(+) T cell priming that to date has not been elucidated. Here we show that CD4(+) T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4(+) T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4(+) T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.  (+info)

Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene. (6/1553)

Receptor activator of NF-kappa B ligand (RANKL)/tumor necrosis factor-related activation induced cytokine (TRANCE)/osteoprotegerin ligand (OPGL)/osteoclast differentiation factor (ODF) is a membrane-bound signal transducer responsible for differentiation and maintenance of osteoclasts. To elucidate the mechanism regulating RANKL/TRANCE/OPGL/ODF gene expression, we cloned the 5'-flanking basic promoter region of the mouse RANKL/TRANCE/OPGL/ODF gene and characterized it by transient transfection studies and genomic Southern blot analysis. Inverted TATA- and CAAT-boxes and a putative Cbfa1/Osf2/AML3 binding domain constituted the basic promoter structure. The repeated half-sites for the vitamin D3 (VitD3) and glucocorticoid receptors were located at -935 and -640, respectively. Transient transfection studies revealed that short-term treatment with 1alpha,25(OH)2 VitD3 or dexamethasone increased luciferase activity up to 204% and 178%, respectively; on the other hand, treatment with dibutyryl cyclic AMP did not affect the promoter activity. Since the expression of Cbfa1/Osf2/AML3 is also regulated by VitD3, 1alpha,25(OH)2 VitD3 might affect RANKL/TRANCE/OPGL/ODF gene expression both directly and indirectly. CpG methylation was observed dominantly in mouse stromal cells, ST2, of a later passage which ceased to support in vitro osteoclastogenesis, suggesting that the methylation status of the CpG loci in the RANKL/TRANCE/OPGL/ODF gene promoter may be one of the influential cis-regulating factors.  (+info)

Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. (7/1553)

Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a member of the TNF family, is a dendritic cell survival factor and is essential for osteoclastogenesis and osteoclast activation. In this report we demonstrate (i) that TRANCE, like TNF-alpha, is made as a membrane-anchored precursor, which is released from the plasma membrane by a metalloprotease; (ii) that soluble TRANCE has potent dendritic cell survival and osteoclastogenic activity; (iii) that the metalloprotease-disintegrin TNF-alpha convertase (TACE) can cleave immunoprecipitated TRANCE in vitro in a fashion that mimics the cleavage observed in tissue culture cells; and (iv) that in vitro cleavage of a TRANCE ectodomain/CD8 fusion protein and of a peptide corresponding to the TRANCE cleavage site by TACE occurs at the same site that is used when TRANCE is shed from cells into the supernatant. We propose that the TRANCE ectodomain is released from cells by TACE or a related metalloprotease-disintegrin, and that this release is an important component of the function of TRANCE in bone and immune homeostasis.  (+info)

The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. (8/1553)

Osteoprotegerin (OPG) and OPG-ligand (OPGL) potently inhibit and stimulate, respectively, osteoclast differentiation (Simonet, W.S., D.L. Lacey, C.R. Dunstan, M. Kelley, M.-S. Chang, R. Luethy, H.Q. Nguyen, S. Wooden, L. Bennett, T. Boone, et al. 1997. Cell. 89:309-319; Lacey, D.L., E. Timms, H.-L. Tan, M.J. Kelley, C.R. Dunstan, T. Burgess, R. Elliott, A. Colombero, G. Elliott, S. Scully, et al. 1998. Cell. 93: 165-176), but their effects on mature osteoclasts are not well understood. Using primary cultures of rat osteoclasts on bone slices, we find that OPGL causes approximately sevenfold increase in total bone surface erosion. By scanning electron microscopy, OPGL-treated osteoclasts generate more clusters of lacunae on bone suggesting that multiple, spatially associated cycles of resorption have occurred. However, the size of individual resorption events are unchanged by OPGL treatment. Mechanistically, OPGL binds specifically to mature OCs and rapidly (within 30 min) induces actin ring formation; a marked cytoskeletal rearrangement that necessarily precedes bone resorption. Furthermore, we show that antibodies raised against the OPGL receptor, RANK, also induce actin ring formation. OPGL-treated mice exhibit increases in blood ionized Ca++ within 1 h after injections, consistent with immediate OC activation in vivo. Finally, we find that OPG blocks OPGL's effects on both actin ring formation and bone resorption. Together, these findings indicate that, in addition to their effects on OC precursors, OPGL and OPG have profound and direct effects on mature OCs and indicate that the OC receptor, RANK, mediates OPGL's effects.  (+info)

In the medical field, RANK ligand, also known as osteoprotegerin ligand (OPGL), is a protein that plays a crucial role in bone remodeling and the regulation of bone homeostasis. It is a member of the tumor necrosis factor (TNF) superfamily of cytokines and is primarily produced by osteoblasts, which are cells responsible for bone formation. RANK ligand binds to a receptor called RANK (receptor activator of nuclear factor kappa-B) on the surface of osteoclasts, which are cells responsible for bone resorption or breakdown. The binding of RANK ligand to RANK triggers a signaling cascade that leads to the activation and differentiation of osteoclasts, promoting bone resorption. In addition to its role in bone remodeling, RANK ligand has been implicated in various other physiological and pathological processes, including inflammation, cancer, and autoimmune diseases. Therefore, targeting RANK ligand has become an attractive therapeutic strategy for the treatment of these conditions.

Receptor Activator of Nuclear Factor-kappa B (RANK) is a protein that plays a critical role in the regulation of bone remodeling and the development of osteoclasts, which are cells responsible for breaking down bone tissue. RANK is expressed on the surface of osteoclast precursors and is activated by binding to its ligand, RANKL (Receptor Activator of Nuclear Factor-kappa B Ligand), which is produced by osteoblasts and other cells in the bone microenvironment. Activation of RANK by RANKL leads to the recruitment and activation of the transcription factor NF-kappaB, which promotes the differentiation and survival of osteoclasts. Dysregulation of RANK/RANKL signaling has been implicated in a number of bone disorders, including osteoporosis, osteopetrosis, and rheumatoid arthritis.

Osteoprotegerin (OPG) is a protein that plays a critical role in bone metabolism and is involved in the regulation of bone resorption, or the breakdown of bone tissue. It is produced by osteoblasts, which are cells responsible for bone formation, and by other cells in the body, including immune cells and endothelial cells. OPG acts as a decoy receptor for the receptor activator of nuclear factor kappa-B ligand (RANKL), a protein that stimulates osteoclasts, the cells responsible for bone resorption. By binding to RANKL, OPG prevents it from binding to its target receptor on osteoclasts, thereby inhibiting osteoclast activation and bone resorption. In the medical field, OPG has been studied for its potential role in the treatment of osteoporosis, a condition characterized by low bone density and an increased risk of fractures. OPG has also been studied in the context of other bone-related disorders, such as Paget's disease of bone and multiple myeloma, as well as in the regulation of bone metabolism in other organs, such as the kidneys and the lungs.

Receptors, Tumor Necrosis Factor (TNF receptors) are proteins found on the surface of cells that bind to the cytokine tumor necrosis factor (TNF). TNF is a signaling molecule that plays a role in the immune response and inflammation. There are two main types of TNF receptors: TNFR1 (also known as TNFRp55) and TNFR2 (also known as TNFRp75). TNFR1 is expressed on most cell types and is involved in the regulation of cell survival, proliferation, and apoptosis (programmed cell death). TNFR2 is primarily expressed on immune cells and is involved in immune cell activation and differentiation. TNF receptors can be activated by binding to TNF, which triggers a signaling cascade within the cell. This signaling cascade can lead to a variety of cellular responses, including the activation of immune cells, the induction of inflammation, and the promotion of cell survival or death. Abnormalities in TNF receptor signaling have been implicated in a number of diseases, including autoimmune disorders, inflammatory diseases, and certain types of cancer. As a result, TNF receptors are the targets of several drugs used to treat these conditions, including TNF inhibitors.

Osteitis deformans, also known as Paget's disease of bone, is a chronic disorder of the skeletal system characterized by increased bone turnover and abnormal bone remodeling. It typically affects older adults and is more common in men than women. The disease is characterized by periods of increased bone resorption (breakdown) and formation (rebuilding), leading to thickening and weakening of the bone. This can cause bone pain, deformities, and an increased risk of fractures. The exact cause of osteitis deformans is not fully understood, but it is thought to be related to genetic and environmental factors. Treatment typically involves medications to slow down bone turnover and relieve symptoms, as well as physical therapy to maintain bone strength and prevent fractures.

Receptors, Cytoplasmic and Nuclear are proteins that are found within the cytoplasm and nucleus of cells. These receptors are responsible for binding to specific molecules, such as hormones or neurotransmitters, and triggering a response within the cell. This response can include changes in gene expression, enzyme activity, or other cellular processes. In the medical field, understanding the function and regulation of these receptors is important for understanding how cells respond to various stimuli and for developing treatments for a wide range of diseases.

Membrane glycoproteins are proteins that are attached to the cell membrane through a glycosyl group, which is a complex carbohydrate. These proteins play important roles in cell signaling, cell adhesion, and cell recognition. They are involved in a wide range of biological processes, including immune response, cell growth and differentiation, and nerve transmission. Membrane glycoproteins can be classified into two main types: transmembrane glycoproteins, which span the entire cell membrane, and peripheral glycoproteins, which are located on one side of the membrane.

Bone resorption is a process in which bone tissue is broken down and removed by osteoclasts, which are specialized cells in the bone marrow. This process is a normal part of bone remodeling, which is the continuous process of bone formation and resorption that occurs throughout life. Bone resorption is necessary for the growth and development of bones, as well as for the repair of damaged bone tissue. However, excessive bone resorption can lead to a number of medical conditions, including osteoporosis, which is a condition characterized by weak and brittle bones that are prone to fractures. Other conditions that can be caused by excessive bone resorption include Paget's disease of bone, which is a disorder that causes the bones to become abnormally thick and weak, and hyperparathyroidism, which is a condition in which the parathyroid glands produce too much parathyroid hormone, which can lead to increased bone resorption. Bone resorption can also be caused by certain medications, such as corticosteroids, and by certain medical conditions, such as cancer and rheumatoid arthritis. In these cases, bone resorption can lead to a loss of bone mass and density, which can increase the risk of fractures and other complications.

Osteolysis is a medical condition characterized by the breakdown and destruction of bone tissue. It can occur in various parts of the body, including the bones of the spine, pelvis, and extremities. Osteolysis can be caused by a variety of factors, including infection, inflammation, trauma, and certain medical conditions such as osteoporosis, cancer, and metabolic disorders. It can also be a complication of certain medical treatments, such as chemotherapy or radiation therapy. The symptoms of osteolysis may include pain, swelling, and tenderness in the affected area, as well as weakness or instability in the affected joint. In severe cases, osteolysis can lead to the formation of bone cysts or tumors, which can cause further complications. Treatment for osteolysis depends on the underlying cause and the severity of the condition. In some cases, medications may be used to manage pain and inflammation, while in other cases, surgery may be necessary to remove damaged bone tissue or stabilize the affected joint. In some cases, physical therapy or other forms of rehabilitation may also be recommended to help improve strength and mobility.

In the medical field, carrier proteins are proteins that transport molecules across cell membranes or within cells. These proteins bind to specific molecules, such as hormones, nutrients, or waste products, and facilitate their movement across the membrane or within the cell. Carrier proteins play a crucial role in maintaining the proper balance of molecules within cells and between cells. They are involved in a wide range of physiological processes, including nutrient absorption, hormone regulation, and waste elimination. There are several types of carrier proteins, including facilitated diffusion carriers, active transport carriers, and ion channels. Each type of carrier protein has a specific function and mechanism of action. Understanding the role of carrier proteins in the body is important for diagnosing and treating various medical conditions, such as genetic disorders, metabolic disorders, and neurological disorders.

Glycoproteins are a type of protein that contains one or more carbohydrate chains covalently attached to the protein molecule. These carbohydrate chains are made up of sugars and are often referred to as glycans. Glycoproteins play important roles in many biological processes, including cell signaling, cell adhesion, and immune response. They are found in many different types of cells and tissues throughout the body, and are often used as markers for various diseases and conditions. In the medical field, glycoproteins are often studied as potential targets for the development of new drugs and therapies.

Osteoporosis is a medical condition characterized by a decrease in bone density and strength, making bones more fragile and prone to fractures. It is a common condition, particularly in older adults, and can affect both men and women. In osteoporosis, the bones become porous and brittle, which can lead to fractures even with minor trauma or falls. The most common sites for osteoporosis-related fractures are the spine, hip, and wrist. Osteoporosis is often diagnosed through a bone density test, which measures the amount of bone mineral density in the hip and spine. Risk factors for osteoporosis include age, gender, family history, smoking, excessive alcohol consumption, and certain medical conditions such as thyroid disease or rheumatoid arthritis. Treatment for osteoporosis typically involves medications to increase bone density and reduce the risk of fractures, as well as lifestyle changes such as regular exercise and a healthy diet rich in calcium and vitamin D.

Bone neoplasms are abnormal growths or tumors that develop in the bones. They can be either benign (non-cancerous) or malignant (cancerous). Benign bone neoplasms are usually slow-growing and do not spread to other parts of the body, while malignant bone neoplasms can be invasive and spread to other parts of the body through the bloodstream or lymphatic system. There are several types of bone neoplasms, including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and multiple myeloma. These tumors can affect any bone in the body, but they are most commonly found in the long bones of the arms and legs, such as the femur and tibia. Symptoms of bone neoplasms may include pain, swelling, and tenderness in the affected bone, as well as bone fractures that do not heal properly. Diagnosis typically involves imaging tests such as X-rays, MRI scans, and CT scans, as well as a biopsy to examine a sample of the tumor tissue. Treatment for bone neoplasms depends on the type and stage of the tumor, as well as the patient's overall health. Options may include surgery to remove the tumor, radiation therapy to kill cancer cells, chemotherapy to shrink the tumor, and targeted therapy to block the growth of cancer cells. In some cases, a combination of these treatments may be used.

In the medical field, "bone and bones" typically refers to the skeletal system, which is made up of bones, cartilage, ligaments, tendons, and other connective tissues. The skeletal system provides support and structure to the body, protects vital organs, and allows for movement through the use of muscles. Bones are the main component of the skeletal system and are responsible for providing support and protection to the body. There are 206 bones in the human body, which are classified into four types: long bones, short bones, flat bones, and irregular bones. Long bones, such as the femur and humerus, are cylindrical in shape and are found in the arms and legs. Short bones, such as the carpals and tarsals, are cube-shaped and are found in the wrists and ankles. Flat bones, such as the skull and ribs, are thin and flat and provide protection to vital organs. Irregular bones, such as the vertebrae and pelvis, have complex shapes that allow for specific functions. Overall, the bone and bones of the skeletal system play a crucial role in maintaining the health and function of the human body.

CD40 Ligand (CD40L) is a protein that is expressed on the surface of activated T cells, B cells, and dendritic cells. It plays a critical role in the immune response by binding to the CD40 receptor on the surface of antigen-presenting cells (APCs), such as dendritic cells and B cells. This interaction triggers a signaling cascade that leads to the activation and proliferation of APCs, as well as the differentiation of T cells into effector cells that can attack infected cells or cancer cells. CD40L is also involved in the regulation of inflammation and the development of autoimmunity. In the medical field, CD40L is being studied as a potential target for the treatment of various diseases, including cancer, autoimmune disorders, and infectious diseases.

Cell differentiation is the process by which cells acquire specialized functions and characteristics during development. It is a fundamental process that occurs in all multicellular organisms, allowing cells to differentiate into various types of cells with specific functions, such as muscle cells, nerve cells, and blood cells. During cell differentiation, cells undergo changes in their shape, size, and function, as well as changes in the proteins and other molecules they produce. These changes are controlled by a complex network of genes and signaling pathways that regulate the expression of specific genes in different cell types. Cell differentiation is a critical process for the proper development and function of tissues and organs in the body. It is also involved in tissue repair and regeneration, as well as in the progression of diseases such as cancer, where cells lose their normal differentiation and become cancerous.

Fas Ligand Protein (FasL) is a type of protein that plays a crucial role in the regulation of the immune system. It is also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or Apo-2L. FasL is expressed on the surface of certain immune cells, such as natural killer (NK) cells and cytotoxic T cells, and it binds to a protein receptor called Fas (also known as CD95) on the surface of target cells. When FasL binds to Fas, it triggers a process called apoptosis, which is a form of programmed cell death. In the context of the immune system, FasL is important for eliminating infected or cancerous cells. However, when FasL is expressed at high levels, it can also contribute to autoimmune diseases and tissue damage. Therefore, the regulation of FasL expression is tightly controlled in the body.

In the medical field, "Cells, Cultured" refers to cells that have been grown and maintained in a controlled environment outside of their natural biological context, typically in a laboratory setting. This process is known as cell culture and involves the isolation of cells from a tissue or organism, followed by their growth and proliferation in a nutrient-rich medium. Cultured cells can be derived from a variety of sources, including human or animal tissues, and can be used for a wide range of applications in medicine and research. For example, cultured cells can be used to study the behavior and function of specific cell types, to develop new drugs and therapies, and to test the safety and efficacy of medical products. Cultured cells can be grown in various types of containers, such as flasks or Petri dishes, and can be maintained at different temperatures and humidity levels to optimize their growth and survival. The medium used to culture cells typically contains a combination of nutrients, growth factors, and other substances that support cell growth and proliferation. Overall, the use of cultured cells has revolutionized medical research and has led to many important discoveries and advancements in the field of medicine.

In the medical field, binding sites refer to specific locations on the surface of a protein molecule where a ligand (a molecule that binds to the protein) can attach. These binding sites are often formed by a specific arrangement of amino acids within the protein, and they are critical for the protein's function. Binding sites can be found on a wide range of proteins, including enzymes, receptors, and transporters. When a ligand binds to a protein's binding site, it can cause a conformational change in the protein, which can alter its activity or function. For example, a hormone may bind to a receptor protein, triggering a signaling cascade that leads to a specific cellular response. Understanding the structure and function of binding sites is important in many areas of medicine, including drug discovery and development, as well as the study of diseases caused by mutations in proteins that affect their binding sites. By targeting specific binding sites on proteins, researchers can develop drugs that modulate protein activity and potentially treat a wide range of diseases.

In the medical field, an amino acid sequence refers to the linear order of amino acids in a protein molecule. Proteins are made up of chains of amino acids, and the specific sequence of these amino acids determines the protein's structure and function. The amino acid sequence is determined by the genetic code, which is a set of rules that specifies how the sequence of nucleotides in DNA is translated into the sequence of amino acids in a protein. Each amino acid is represented by a three-letter code, and the sequence of these codes is the amino acid sequence of the protein. The amino acid sequence is important because it determines the protein's three-dimensional structure, which in turn determines its function. Small changes in the amino acid sequence can have significant effects on the protein's structure and function, and this can lead to diseases or disorders. For example, mutations in the amino acid sequence of a protein involved in blood clotting can lead to bleeding disorders.

TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a protein that plays a role in the regulation of programmed cell death, also known as apoptosis. It is a member of the tumor necrosis factor (TNF) superfamily of cytokines and is expressed by a variety of cells, including immune cells and some cancer cells. TRAIL binds to specific receptors on the surface of target cells, triggering a cascade of events that ultimately leads to the activation of caspases, a family of proteases that play a central role in the execution of apoptosis. TRAIL-induced apoptosis is a highly selective process, as it primarily targets cells that express the TRAIL receptors, while sparing normal cells. TRAIL has been studied as a potential therapeutic agent for the treatment of various types of cancer, as many cancer cells are highly sensitive to TRAIL-induced apoptosis. However, some cancer cells have developed resistance to TRAIL, which has limited its clinical utility. Despite this, ongoing research is exploring ways to overcome TRAIL resistance and enhance its anti-cancer effects.

CD30 ligand, also known as CD153 or tumor necrosis factor superfamily member 8 (TNFSF8), is a protein that plays a role in the immune system. It is expressed on the surface of activated T cells, B cells, and some types of cancer cells. CD30 ligand binds to a protein called CD30, which is found on the surface of activated T cells and some types of cancer cells. This interaction can stimulate the growth and survival of CD30-expressing cells, and it has been implicated in the development and progression of certain types of cancer, such as Hodgkin's lymphoma and anaplastic large cell lymphoma. CD30 ligand is also being studied as a potential target for cancer therapy.

Ligands and metal ions can be ordered in many ways; one ranking system focuses on ligand 'hardness' (see also hard/soft acid/ ... Bridging carbonyl Crystal field theory DNA binding ligand Inorganic chemistry Josiphos ligands Ligand dependent pathway Ligand ... A ligand exchange (also ligand substitution) is a type of chemical reaction in which a ligand in a compound is replaced by ... Example is alkoxy ligands( which is regularly known as X ligand too). L ligands are derived from charge-neutral precursors and ...
Castellano D, Sepulveda JM, García-Escobar I, Rodriguez-Antolín A, Sundlöv A, Cortes-Funes H (2011). "The role of RANK-ligand ... RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls ... Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 ( ... Some studies suggest, since RANK-RANKL pathway regulates calcium release and homeostasis, RANK-RANKL signal could invertedly ...
Schoppet M, Preissner KT, Hofbauer LC (April 2002). "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism ... namely osteoprotegerin and RANK ligand. Note that these molecules also regulate differentiation of the osteoclast. An ... through RANK. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs and is not upregulated. ... Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage ...
... is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast ... The RANK-RANKL complex forms a heterohexameric complex. Only two of the four RANK CRDs are in direct contact with the RANKL. ... Sattler AM, Schoppet M, Schaefer JR, Hofbauer LC (2004). "Novel aspects on RANK ligand and osteoprotegerin in osteoporosis and ... RANK is expressed in key regions of the brain associated with thermoregulation. Inactivation of RANK in these regions causes a ...
According to one ligand ranking scale, phen is a weaker donor than bipy. Several homoleptic complexes are known of the type [M( ... Such bulky ligands also favor trigonal or tetrahedral coordination at the metal. Phen itself form complexes of the type [M(phen ... Abbreviated "phen", it is used as a ligand in coordination chemistry, forming strong complexes with most metal ions. It is ... A variety of substituted derivatives of phen have been examined as ligands. Substituents at the 2,9 positions confer protection ...
Sundaram K, Mani SK, Kitatani K, Wu K, Pestell RG, Reddy SV (April 2008). "DACH1 negatively regulates the human RANK ligand ...
RANK is activated by RANKL (the RANK-Ligand), which exists as cell surface molecules on osteoblasts. Activation of RANK by ... Denosumab is an inhibitor of RANKL (receptor activator of nuclear factor kappa-Β ligand), which works by decreasing the ... May 2012). "Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab". Nature Reviews. Drug ... EntrezGene 8600 TNFSF11 tumor necrosis factor (ligand) superfamily, member 11; Homo sapiens also known as RANKL. This protein ...
... which facilitates osteoclasts maturation upon binding of RANK ligand (RANKL). Binding of RANK ligand mediates the RANK/RANKL/ ... The TNFRSF11A gene is present in chromosome locus 18q21.33, which encodes for the receptor activator of NF-κB (RANK). RANK is ... Missense mutation was reported to be present in multiple patients and ranked disease-causing by MutationTaster. This insertion ... and instead produce a truncated isoform of the RANK protein. The mutated protein has structural defects hence hinders normal ...
For men with prostate cancer and bone metastases zoledronic acid (a bisphosphonate) and denosumab (a RANK-ligand-inhibitor) ... Cochrane Urology Group) (December 2020). "Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone ...
Li L, Wang B, Meroueh SO (September 2011). "Support vector regression scoring of receptor-ligand complexes for rank-ordering ... Ligand active conformation - three-dimensional shape of the ligand when bound to the protein Binding-mode - orientation of the ... Counting may be based on the number of ligand and receptor atoms in contact with each other or by calculating the change in ... A perfect scoring function would be able to predict the binding free energy between the ligand and its target. But in reality ...
Each ligand has a different potency, measured as increased cyclic AMP (cAMP) concentration after the binding event. The rank ... The primary endogenous ligands of the human TAAR1 (hTAAR1) receptor, by rank order of potency, are: tyramine > β-phenethylamine ... TAAR1 and its homologues have ligand pocket vectors that utilize sets of 35 amino acids known to be involved directly in ... E.g., a TAAR1 ligand which can easily pass through the norepinephrine transporter, but not the serotonin transporter, will ...
RANK) and its ligand (RANKL) in human deciduous teeth". Calcified Tissue International. 71 (1): 45-52. doi:10.1007/s00223-001- ... Receptive activator of nuclear factor kappa-B ligand (RANKL), also called osteoclast differentiation factor (ODF) and ... March 1998). "Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is ... is a main mediator in receptor activator of nuclear factor-kappaB ligand-dependent osteoclastogenesis induced by Porphyromonas ...
The HEP scale ranks ligands on the basis of the 13C NMR shift of a reference ligand. Lever's electronic parameter ranking is ... Several other scales have been proposed for the ranking of the donor properties of ligands. ... ligands have been ranked according to IR data recorded on cis-[RhCl(NHC)(CO)2] complexes. Metal carbonyl Tolman cone angle ... Another scale evaluated ligands on the basis of the redox couples of [Cr(CO)5L]0/+. In a treatment akin to the TEP analysis, ...
Mechanism of action: The drug binds to receptor activator nuclear factor κB ligand (RANKL), preventing the interaction with ... RANK. It does not bind to bone and its effect on bone diminishes in 9 months. Osteonecrosis of the jaw has been identified as ...
"Functional role for heat shock factors in the transcriptional regulation of human RANK ligand gene expression in stromal/ ...
These genes include osteocalcin, osteopontin, bone sialoprotein, osteonectin, RANK ligand (NF-κB receptor activator) and ...
This is based on the notion that increased expression of RANK-ligands by stromal cells plays a role in tumor pathogenesis. ... More recently, humanized monoclonal antibodies such as Denosumab targeting the RANK ligand have been employed in treatment of ... Huang , Xu J, Wood DJ, Zheng MH (2000). "Gene Expression of Osteoprotegerin Ligand, Osteoprotegerin, and REceptor Activator of ...
... a novel mutation in TGFβ1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand. ... Extracellular ligand disorders, Skeletal disorders, Rare diseases, Autosomal dominant disorders). ...
Vitamin D, parathyroid hormone and stimulation from osteocytes induce osteoblasts to increase secretion of RANK-ligand and ... Osteoprotegerin is secreted by osteoblasts and is able to bind RANK-L, inhibiting osteoclast stimulation. Osteoblasts can also ...
... and other evidence suggests an intrinsic hyperresponsive reaction to vitamin D and RANK ligand is the cause.[citation needed] ... Paget's disease of bone is associated with mutations in RANK. Receptor Activator of Nuclear Factor κ B (RANK), which is a type ... Whyte, M. P. (1 April 2006). "Paget's Disease of Bone and Genetic Disorders of RANKL/OPG/RANK/NF- B Signaling". Annals of the ... Two genes, SQSTM1 and RANK, and specific regions of chromosome 5 and 6 are associated with Paget's disease of bone. Genetic ...
Osteoprotegerin (OPG), which is a decoy receptor homolog for RANK ligand (RANKL), inhibits RANK by binding to RANKL, and, thus ... RANKL acts through its receptor RANK, which in turn promotes NF-κB, RANKL normally works by enabling the differentiation of ... Baud'huin M, Lamoureux F, Duplomb L, Rédini F, Heymann D (September 2007). "RANKL, RANK, osteoprotegerin: key partners of ... RANK), which is a type of TNFR, is a central activator of NF-κB. ...
The steric properties of phosphine ligands can be ranked by their Tolman cone angle or percent buried volume. An important ... Phosphine ligands are usually "spectator" rather than "actor" ligands. They generally do not participate in reactions, except ... also function as ligands. Such ligands are less basic and have small cone angles. These complexes are susceptible to ... Phosphine ligands are also π-acceptors. Their π-acidity arises from overlap of P-C σ* anti-bonding orbitals with filled metal ...
32, Issue 1, 1-20 Jagger BR, Lee CT, Amaro RE "Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning ... blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies.", J Comput Aided Mol Des, 2018 ...
When the receptor is activated through PTH binding, osteoblasts express RANKL (Receptor Activator of Nuclear Factor kB Ligand ... which binds to RANK (Receptor Activator of Nuclear Factor kB) on osteoclasts. This turns on osteoclasts to ultimately increase ... "Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation". The ...
Protein-directed DCC provides a way to generate, identify and rank novel protein ligands, and therefore have huge potential in ... This strategy is useful for the investigation of the optimal ligand stereochemistry to the binding site of the target protein. ... Thompson, Major C.; Busch, Daryle H. (1964-01-01). "Reactions of Coordinated Ligands. VI. Metal Ion Control in the Synthesis of ... Thompson, Major C.; Busch, Daryle H. (1962-05-01). "Reactions of Coördinated Ligands. II. Nickel(II) Complexes of Some Novel ...
RANKL is a member of the TNF superfamily of ligands. Through binding to the RANK receptor it activates various molecules, like ... The RANKL/RANK signaling pathway regulates osteoclastogenesis, as well as, the survival and activation of osteoclasts. ... However, in the presence of Activin A, a TGF-β ligand, it causes the formation of mesoderm and neuroectoderm. Phosphorylation ... The WNT pathway allows β-catenin function in gene transcription, once the interaction between WNT ligand and G protein-coupled ...
Ligand executives, former high ranking-SEC lawyer Brad Bondi and congressmen Duncan Hunter subsequently lobbied the U.S. ... "Ligand to pay $12.2 million to settle lawsuits". The San Diego Union-Tribune. Retrieved 2018-09-12. "Ligand Announces Recently ... "Ligand loses its listing on Nasdaq". The San Diego Union-Tribune. Retrieved 2018-09-12. "Ligand Announces SEC Investigation". ... LGND)". Ligand. Retrieved 2018-09-12. Bigelow, Bruce (March 25, 2011). "San Diego's Ligand Takes Advantage of the Great ...
... correct energy-ranking of docked ligand poses, correct rank-ordering of active and inactive compounds during virtual screening ... Å RMSD from the reference ligand coordinates) for a set of protein-ligand complexes extracted from PDB. A set of 407 protein- ... extra precision protein-ligand docking and calculation of free energy of ligand binding. Original docking algorithm provides a ... Efficiency of ligand docking and binding energy estimations achieved by Lead Finder are due to docking algorithm and extra ...
... and returns a number indicating the likelihood that the pose represents a favorable binding interaction and ranks one ligand ... In this approach, the protein and the ligand are separated by some physical distance, and the ligand finds its position into ... Most docking programs in use account for the whole conformational space of the ligand (flexible ligand), and several attempt to ... orientation of a ligand that binds to a particular protein of interest. However, since both the ligand and the protein are ...
TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Mutations in MAP3K7IP2 have been associated ... "Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a ... signaling complex containing RANK, TAB2, and TRAF6". Mol. Cell. Biol. 22 (4): 992-1000. doi:10.1128/MCB.22.4.992-1000.2002. PMC ...
Denosumab injection (Xgeva) is used Denosumab injection is in a class of medications called RANK ligand inhibitors. It works to ... Prolia works by blocking a protein called RANK (receptor activator of nuclear factor kappa beta) and helps prevent bone cells ...
RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1ß- and RNA-dependent co-activator of osteoclast gene expression. ... RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1ß- and RNA-dependent co-activato ... AP-1; H3K27ac; HDAC3; NCoR; NF-κB; PGC1ß; RANK; co-activator; deacetylation; gene expression; non-coding RNA; osteoclast ... Mechanistically, RANK signaling promotes RNA-dependent interaction of the transcriptional co-activator PGC1ß with the NCoR/ ...
Producing chemotactic factors, as well as RANK ligand (RANKL; a transmembrane or soluble protein essential for the formation, ...
RANK ligand as a potential target for breast cancer prevention in BRCA1 mutation carriers. Nature Med. 2016 22(8):933-939. PMID ... This work led to the discovery of RANK-positive progenitors as a target for breast cancer prevention in BRCA1 mutation carriers ...
Fosamax, Boniva, Reclast and Actonel are bisphosphonates; Forteo is a parathyroid hormone; and Prolia is a RANK ligand ...
B (RANK), its ligand RANKL, and the protein osteoprotegerin (OPG) [29]. RANKL is a membrane-bound protein expressed primarily ... RANK-Fc (a recombinant soluble protein consisting of extracellular domain of RANK coupled with the Fc domain of human IgG) was ... B ligand (RANKL), and tumor necrosis factor (TNF-α) which are involved in the stimulation of osteoclast differentiation and ... B. F. Boyce and L. Xing, "Functions of RANKL/RANK/OPG in bone modeling and remodeling," Archives of Biochemistry and Biophysics ...
The ability to rank covalent molecular binders with similar warheads using SILCS ligand grid free energy (LGFE) ranking was ... Integrated Covalent Drug Design Workflow Using Site Identification by Ligand Competitive Saturation J Chem Theory Comput. 2023 ... To facilitate the design of this class of ligands, computational methods can be used to help identify reactive nucleophilic ... site identification by ligand competitive saturation) that intrinsically considers protein flexibility, functional group, and ...
Denosumab is a fully human monoclonal antibody that targets RANK Ligand (an essential mediator of cells that break down bone) ... Denosumab is a fully human monoclonal antibody that targets RANK Ligand and is being investigated for its potential to prevent ... Denosumab is the first late-stage investigational therapy that specifically inhibits RANK Ligand, an essential mediator of the ...
As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages ... The interaction between RANK and its ligand, RANKL, a cytokine member of the tumor necrosis factor superfamily, was first ... Receptor activator of nuclear factor kappa-B ligand (RANKL)/RANK signaling promotes cancer-related inflammation through M2 ... mRNA expression of CCL5, MMP1, and MMP25 on CD163+ CD206+ Arg1+ RANK+ M2 macrophages is augmented by stimulation with sRANKL. ...
By using the Maximum Entropy Method, we will be able to enhance the specificity of scoring functions for ligand ranking. Second ... First is to design a fully automated platform for structure-based ligand virtual screening featuring an information theory- ...
Statistical potential for modeling and ranking of protein-ligand interactions. J Chem Inf Model. 2011 Dec 27; 51(12):3078-92. ... because their ligands are very similar). Since the new relationships are articulated by ligands, they may be directly tested ... structure-based ligand discovery). Two ongoing projects are 1. Developing new computational methods for ligand discovery and 2 ... Structure-based ligand discovery for the protein-protein interface of chemokine receptor CXCR4. Proc Natl Acad Sci U S A. 2012 ...
RANK binds to transmembrane protein nuclear factor-κB receptor activating factor ligand (RANKL) to activate RANK/RANKL, TRAF6/ ... It is worth noting that BMAs can also express RANKL, suggesting that BMAs may participate in bone remodeling through RANK/RANKL ... OPG can inhibit OC differentiation by competing with RANKL and binding to RANK. Actin binding protein L-plastin (LPL) can ... However, osteoprotegerin (OPG), a natural antagonist of the RANKL-RANK pathway, is a glycoprotein that can inhibit OC ...
ONJ has also been associated with denosumab, a monoclonal antibody that inhibits RANK ligand-stimulation of osteoclast function ...
Thiol ligands modify metal nanocluster structures and optical properties. Metal nanoclusters are tiny, crystalline structures ... Updated Daily.( ... sorted: rank/1w)(... continued page 2) ...
... polarisation model which affords a simple assessment of Ln ion donor atom preference and ranks the axial second-order ligand ... Measurements of the free energy change associated with axial ligand exchange in a cationic europium tetraamide complex, [Eu( ... axial donor polarisability determines ligand field and cation donor preference.. Dalton Transactions, 7 pp. 1264-1271. ... and nine-coordinate axially symmetric complexes based on cyclen including aza-carboxylate ligands (e.g. DOTA), phosphonates ( ...
Top-ranked cinnamic acids were ranked based on the Δ G binding values between the ligands and the receptors active site. ... Ranking. CiteScore. 2.5. 2022, Scopus (Elsevier B.V., 2023). SCImago Journal Rank. 0.306. 2022, SJR (Scimago Lab, 2023; Data ... AutoDock Vina was used to calculate the binding affinities between the protein and ligands and to predict most promising ... Interaction modes between top-ranked cinnamic acids and MAPK3 catalytic site were indicated using the Discovery Studio ...
Ranking allows comparison of individual poses of a single ligand, or the comparison of binding modes of different ligands. The ... Scoring - Ranking Binding Modes. Scoring assesses the interaction quality of the complex (ligand and target) of a pose. Poses ... It assesses the binding affinity of any ligand in a binding site, be it from docking or from a crystal structure. SeeSAR is ... The size of the sphere reflects the quantitive contribution to the overall binding affinity of the ligand. By loading a ...
A couple of better-ranked stocks in the overall healthcare sector include Allogene ALLO and Ligand Pharmaceuticals LGND, each ... Zacks Rank & Stocks to Consider. Sarepta currently has a Zacks Rank #3 (Hold). ... Earnings of Ligand beat estimates in one of the last four quarters, while missing the mark on the other three occasions. On ... Ligand Pharmaceuticals Incorporated (LGND) : Free Stock Analysis Report. Sarepta Therapeutics, Inc. (SRPT) : Free Stock ...
Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the ... Indirect paths rank first, with the lowest cost, only in a few snapshots of the ligand-free form of FepA. ... for the ligand-free simulation), respectively 86 ns (with ligand), unrestrained MD run in the NPT ensemble. The MD simulation ... Some widest paths found with a soft penalty are displayed for the ligand-free (70 ns, (A,C)) and complexed (86 ns, (B,D)) forms ...
RANK ligand", ... KW - RANK ligand. UR - http://www.scopus.com/inward/record.url? ...
RANK Ligand RANK Protein use Receptor Activator of Nuclear Factor-kappa B ...
RANK Ligand RANK Protein use Receptor Activator of Nuclear Factor-kappa B ...
RANK Ligand RANK Protein use Receptor Activator of Nuclear Factor-kappa B ...
RANK Ligand RANK Protein use Receptor Activator of Nuclear Factor-kappa B ...
RANK Ligand RANK Protein use Receptor Activator of Nuclear Factor-kappa B ...
Geusens P. The role of RANK ligand/osteoprotegerin in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2012; 4: 225-233. ... Tanaka S. Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways. World J Orthop. 2013; 4: 1-6. ... An HLA-DRB1- coded signal transduction ligand facilitates inflammatory arthritis: a new mechanism of autoimmunity. J Immunol. ... ACPA: Anti-Citrullinated Protein Antibody; ACR: American College of Rheumatology; APRIL: A Proliferation-Inducing Ligand; BAFFR ...
RANK ligand (RANKL) inhibitor. Denosumab. Prolia™. Injection. Every 6 Months. *Estrogen is also available in other preparations ...
  • As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages promotes the production of chemokines and proinflammatory cytokines to maintain the immunosuppressive tumor environment of extramammary Paget's disease (EMPD). (iiarjournals.org)
  • Since EMPD is a skin adenocarcinoma of apocrine gland origin that expresses high levels of RANKL and matrix metalloproteinase (MMP) 7, and EMPD is associated with the presence of RANK + M2 macrophages, we hypothesized that tumor-associated macrophages (TAMs) in adenocarcinomas such as PCAC might also express RANKL and MMP7. (iiarjournals.org)
  • Conclusion: Our study suggests that the RANKL/RANK pathway contributes to the development and maintenance of the immunosuppressive tumor microenvironment and denosumab may be a promising adjuvant therapy targeting TAMs in cancer of apocrine origin. (iiarjournals.org)
  • RANK binds to transmembrane protein nuclear factor-κB receptor activating factor ligand (RANKL) to activate RANK/RANKL, TRAF6/RANKL/MAPKs, TRAF6/ RANKL/NF-κB, Wnt/RANKL/RANKL, and JAK2/STAT3/RANKL. (frontiersin.org)
  • Osteoprotegerin is one of two receptor proteins that can attach (bind) to a protein called receptor activator of NF-κB ligand (RANKL). (medlineplus.gov)
  • Because RANKL can only bind to one receptor at a time, osteoprotegerin and RANK compete with one another. (medlineplus.gov)
  • When RANKL is bound to RANK, it sets off a series of chemical signals that trigger immature osteoclasts to mature and become fully functional. (medlineplus.gov)
  • By reducing the amount of RANKL that is available to bind to RANK, osteoprotegerin plays a critical role in regulating the process of bone remodeling. (medlineplus.gov)
  • Without osteoprotegerin, RANKL binds only to RANK. (medlineplus.gov)
  • 20. Lossdorfer S, Gotz W, Jager A. Immunohistochemical localization of receptor activator of nuclear factor kappaB (RANK) and its ligand (RANKL) in human deciduous teeth. (bvsalud.org)
  • The ability to rank covalent molecular binders with similar warheads using SILCS ligand grid free energy (LGFE) ranking was also tested for several proteins. (nih.gov)
  • To facilitate the design of this class of ligands, computational methods can be used to help identify reactive nucleophilic residues, frequently cysteines, on a target protein for covalent binding, to test various warhead groups for their potential reactivities, and to predict noncovalent contributions to binding that can facilitate drug-target interactions that are important for binding specificity. (nih.gov)
  • Developing new computational methods for ligand discovery and 2. (ucsf.edu)
  • Developing computational methods to relate receptors by the similarity of their ligands, rather than by protein sequence or structure. (ucsf.edu)
  • This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. (arigobio.com)
  • Many of the signaling pathways that control normal bone homeostasis are at play in pathologic PCa bone metastases, including the receptor activator of nuclear factor-kB/receptor activator of nuclear factor-kB ligand/osteoprotegerin system. (mssm.edu)
  • Prolia works by blocking a protein called RANK (receptor activator of nuclear factor kappa beta) and helps prevent bone cells called osteoclasts from breaking down bone in the body. (medlineplus.gov)
  • For example, Paget's cells release soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) into the tumor microenvironment, stimulating RANK + TAMs to produce CCL17, which recruits Tregs into the lesional skin of patients with extramammary Paget's disease (EMPD) ( 11 , 17 ). (iiarjournals.org)
  • Its differentiation and function are mainly regulated by macrophage colony-stimulating factor (M- CSF), receptor activator of nuclear factor kappa B(RANK) ( 7 ). (frontiersin.org)
  • Immunohistochemical staining of MMP1 and MMP25 as well as chemokine (C-C motif) ligand (CCL) 5 in the lesional skin from five patients with PCAC showed a substantial number of MMP1-bearing cells and MMP25-bearing cells, as well as CCL5-producing cells, that were distributed in the lesional skin. (iiarjournals.org)
  • Ligands in a complex dictate the reactivity of the central atom, including ligand substitution rates, the reactivity of the ligands themselves, and redox. (wikipedia.org)
  • Binding of the metal with the ligands results in a set of molecular orbitals, where the metal can be identified with a new HOMO and LUMO (the orbitals defining the properties and reactivity of the resulting complex) and a certain ordering of the 5 d-orbitals (which may be filled, or partially filled with electrons). (wikipedia.org)
  • Denosumab is a fully human monoclonal antibody that targets RANK Ligand (an essential mediator of cells that break down bone) and is being investigated for its potential to treat and prevent a broad range of bone loss conditions including osteoporosis and bone metastases. (amgen.com)
  • Denosumab is a fully human monoclonal antibody that targets RANK Ligand and is being investigated for its potential to prevent and treat a broad range of bone loss conditions including osteoporosis, bone metastases, treatment-induced bone loss, multiple myeloma and bone erosions in rheumatoid arthritis. (amgen.com)
  • Denosumab is the first late-stage investigational therapy that specifically inhibits RANK Ligand, an essential mediator of the cells that break down bone. (amgen.com)
  • Given the fact that scoring provides a numerical value to each pose, it becomes possible to rank poses. (biosolveit.de)
  • Ranking allows comparison of individual poses of a single ligand, or the comparison of binding modes of different ligands. (biosolveit.de)
  • Flare Free Energy Perturbation (FEP) offers a quantitative method to reliably calculate relative binding affinity, enabling accurate ranking of molecules in a congeneric ligand series. (cresset-group.com)
  • The ligand with the better scoring is more likely to have a better affinity and therefore more likely to bind which is the premise for any pharmacological effect at the target. (biosolveit.de)
  • It assesses the binding affinity of any ligand in a binding site, be it from docking or from a crystal structure. (biosolveit.de)
  • The size of the sphere reflects the quantitive contribution to the overall binding affinity of the ligand. (biosolveit.de)
  • RÉSUMÉ L'objectif de l'étude était d'évaler l'importance clinique du ligand de CD40 soluble (sCD40L) chez des patients atteints d'un carcinome hépatocellulaire (CHC) associé au virus de l'hépatite C (VHC). (who.int)
  • The nature of metal-ligand bonding can range from covalent to ionic. (wikipedia.org)
  • To further aid covalent drug design, we extended a functional group mapping approach based on explicit solvent all-atom molecular simulations (SILCS: site identification by ligand competitive saturation) that intrinsically considers protein flexibility, functional group, and protein desolvation along with functional group-protein interactions. (nih.gov)
  • In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. (wikipedia.org)
  • This means that Flare users can make better, accurately informed decisions around which ligand modifications can achieve the best results, with new molecule designs often ending up quite far away from the initial starting point. (cresset-group.com)
  • ARG81958 Rat sRANK Ligand / TNFSF11 / TRANCE ELISA Kit is an Enzyme Immunoassay kit for the quantification of Rat sRANK Ligand / TNFSF11 / TRANCE in serum, plasma (heparin, EDTA) and cell culture supernatants. (arigobio.com)
  • This changes pharmacological relationships dramatically-targets that would normally be considered sequence neighbors are pushed far apart (because their ligands are dissimilar), whereas other targets that supposedly have nothing to do with one another become neighbors (because their ligands are very similar). (ucsf.edu)
  • Measurements of the free energy change associated with axial ligand exchange in a cationic europium tetraamide complex, [Eu(DOTAMPh)](CF3SO3)3 supported by a simple electrostatic perturbation model, have been interpreted in terms of a predominant donor atom polarisation model which affords a simple assessment of Ln ion donor atom preference and ranks the axial second-order ligand field coefficient. (open.ac.uk)
  • M-CSF binds to the M-CSF receptor, which is promote the proliferation and differentiation of OC and the continuous expression of RANK. (frontiersin.org)
  • Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. (arigobio.com)
  • For the purposes of ranking ligands, however, the properties of the octahedral complexes and the resulting Δo has been of primary interest. (wikipedia.org)
  • The arrangement of the d-orbitals on the central atom (as determined by the 'strength' of the ligand), has a strong effect on virtually all the properties of the resulting complexes. (wikipedia.org)
  • This parameter has been measured directly, by analysing the europium emission spectra for a series of eight- and nine-coordinate axially symmetric complexes based on cyclen including aza-carboxylate ligands (e.g. (open.ac.uk)
  • Metals and metalloids are bound to ligands in almost all circumstances, although gaseous "naked" metal ions can be generated in a high vacuum. (wikipedia.org)
  • Ligands are classified in many ways, including: charge, size (bulk), the identity of the coordinating atom(s), and the number of electrons donated to the metal (denticity or hapticity). (wikipedia.org)
  • According to the molecular orbital theory, the HOMO (Highest Occupied Molecular Orbital) of the ligand should have an energy that overlaps with the LUMO (Lowest Unoccupied Molecular Orbital) of the metal preferential. (wikipedia.org)
  • Les concentrations sériques de sCD40L circulant et d'interleukine 10 circulante ont été analysées à l'aide de la méthode immuno-enzymatique chez 30 patients positifs pour le VHC avec un CHC, chez 30 patients patients positifs pour le VHC avec une cirrhose du foie, et chez 30 volontaires d'âge correspondant en bonne santé avec des anticorps anti-VHC négatifs servant de groupe témoin. (who.int)
  • Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the enterobactin. (nature.com)
  • First is to design a fully automated platform for structure-based ligand virtual screening featuring an information theory-based compound selection. (hhs.gov)
  • This work led to the discovery of RANK-positive progenitors as a target for breast cancer prevention in BRCA1 mutation carriers. (edu.au)
  • Benchmarking experiments can be used to gain confidence that your system is prepared correctly, confirming the predictivity of the method on the target and ligand series of interest. (cresset-group.com)
  • Scoring assesses the interaction quality of the complex (ligand and target) of a pose. (biosolveit.de)
  • The magnitude of Δo is determined by the field-strength of the ligand: strong field ligands, by definition, increase Δo more than weak field ligands. (wikipedia.org)
  • one ranking system focuses on ligand 'hardness' (see also hard/soft acid/base theory). (wikipedia.org)
  • Ligand selection requires critical consideration in many practical areas, including bioinorganic and medicinal chemistry, homogeneous catalysis, and environmental chemistry. (wikipedia.org)
  • A longstanding effort to do so is by exploiting protein structures to predict new reagents and therapeutic leads (structure-based ligand discovery). (ucsf.edu)
  • By using the Maximum Entropy Method, we will be able to enhance the specificity of scoring functions for ligand ranking. (hhs.gov)
  • ARG81958 Rat RANK Ligand / TNFSF11 / TRANCE ELISA Kit results of a typical standard run with optical density reading at 450 nm. (arigobio.com)
  • You can see the complete list of today's Zacks #1 Rank (Strong Buy) stocks here . (yahoo.com)
  • This ordering of ligands is almost invariable for all metal ions and is called spectrochemical series. (wikipedia.org)
  • FEP projects can begin with a much smaller number of ligands than may be required for other methods. (cresset-group.com)
  • Furthermore, the metal-ligand bond order can range from one to three. (wikipedia.org)
  • He showed, among other things, that the formulas of many cobalt(III) and chromium(III) compounds can be understood if the metal has six ligands in an octahedral geometry. (wikipedia.org)
  • Metal ions preferentially bind certain ligands. (wikipedia.org)
  • Statistical analyses were performed using nonparametric Mann-Whitney rank sum test. (cdc.gov)