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.
Metabolic disorder associated with fractures of the femoral neck, vertebrae, and distal forearm. It occurs commonly in women within 15-20 years after menopause, and is caused by factors associated with menopause including estrogen deficiency.
The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.
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.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Infections resulting from the implantation of prosthetic devices. The infections may be acquired from intraoperative contamination (early) or hematogenously acquired from other sites (late).
Prostheses used to partially or totally replace a human or animal joint. (from UMDNS, 1999)
Replacement for a knee joint.
The application of high intensity ultrasound to liquids.
Replacement of the knee joint.
Replacement for a hip joint.
The region of the upper limb between the metacarpus and the FOREARM.
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.

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)

To elucidate the mechanism involved in the oxidized lipid-induced RANKL production in T lymphocytes, we tested a panel of pathway inhibitors, using concentrations that did not affect cell viability. We first investigated the NFκB pathway, based on previous reports showing that this pathway is central to the maturation and activation of osteoclast precursor cells induced by RANK/RANKL binding [44]. Furthermore, the biological activity of MM-LDL and oxidized lipids in several other cell types is mediated, at least in part, through the NFκB pathway [49]. Two different NFκB inhibitors were used, one that blocks the translocation of the active NFκB complex from the cytoplasm into the nucleus (inhibitor 1), and one that prevents the phosphorylation of IκBα (inhibitor 2). We found that the MM-LDL-induced RANKL production by the stimulated T lymphocytes was only modestly reduced when the NFκB pathway was inhibited. (Fig. 3A). By contrast, in the unstimulated T lymphocytes, RANKL production ...
La principale via regolatrice del metabolismo osseo è quella del Receptor Activator Nuclear Factor Kappa B Ligand (RANKL), anche noto come CD254. Questo ligando esiste sia in forma solubile sia di membrana (CD254). Il CD254 è espresso soprattutto dagli Osteoblasti (OBs), le cellule responsabili della formazione dellosso, mentre il suo recettore, RANK, dagli Osteoclasti (OCs), le cellule deputate al riassorbimento. Gli osteoclasti degradano losso dopo lattivazione attraverso il legame del RANKL. Altre cellule possono esprimere il RANKL e lalta espressione del RANKL è associata alla capacità delle cellule di indurre osteolisi. Lanalisi al citofluorimetro ha dimostrato che lespressione della forma di membrana CD254 è up-regolata nei pazienti allesordio B LLA Common rispetto ai controlli fuori terapia o a fine mantenimento. Mediante esperimenti di co-cultura è stata studiata la capacità dei blasti di influenzare il differenziamento dei precursori degli osteoclasti. E stata valutata ...
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rat Receptor Activator Of Nuclear Factor Kappa B Ligand (RANkL) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species ...
TY - JOUR. T1 - Novel inhibitors of RANKL-induced osteoclastogenesis. T2 - Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones. AU - Lee, Chia Chung. AU - Liu, Fei Lan. AU - Chen, Chun Liang. AU - Chen, Tsung Chih. AU - Liu, Feng Cheng. AU - Ahmed Ali, Ahmed Atef. AU - Chang, Deh Ming. AU - Huang, Hsu Shan. PY - 2015/7/23. Y1 - 2015/7/23. N2 - A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced ...
Identification of Nedd9 as a TGF-β-Smad2-3 Target Gene Involved in RANKL-Induced Osteoclastogenesis by Comprehensive Analysis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Vitamin D3, and its most active form 1,25(OH)2D3, are well known to stimulate osteoclastogenesis through stromal cell induction of the receptor activator of nuclear factor kappaB ligand (RANKL). Mitogen activating protein kinase phosphatase-1 (MKP-1) is a phosphatase classically known to negatively regulate the immune response through dephosphorylation of p38, ERK, and JNK activity. Objective: The purpose of this study was to define the role of MKP-1 in genomic 1,25(OH)2D3 signaling and downstream osteoclastogenesis through RANKL. Methods: Primary bone marrow stromal cells (BMSCs) from tibias and femurs of MKP-1-/- and MKP-1+/+ mice were collected. Gene expression was measured using RT-qPCR, protein expression by immunoblot and ELISA in 1,25(OH)2D3 treated cultures. Co-culture osteoclastogenesis assays were conducted as well. Results: RT-qPCR and immunoblot analysis comparing BMSCs revealed that 1,25(OH)2D3-induced VDR, CYP24a1 and RANKL mRNA expression and protein were significantly attenuated ...
The importance of RankL as a key osteoclastogenic factor in bone remodeling is now well established (63). Perhaps most persuasive is the finding through deletion studies in mice that the loss of either RankL or its receptor (Rank) results in a significant deficiency in osteoclast production (20, 37). Indeed, several osteoporotic states in humans have been ascribed to genetic defects in the RANKL/RANK/OPG signaling pathway (68). Thus, although factors separate from RankL are known to play roles in the osteoclastogenic process (35, 63), it is clear that this gene product and its signal transduction pathway are key components. An understanding of the mechanisms whereby this gene is regulated is therefore of paramount importance.. Our studies using ChIP/chip analysis, direct ChIP, and more traditional molecular approaches identified five distinct regions located at significant distances upstream of the TSS that were responsible for regulating the expression of the RankL gene. VDR and RXR localize to ...
Receptor activator of NF-kappaB ligand (RANKL), its signaling receptor RANK, and its decoy receptor osteoprotegerin (OPG) constitute a molecular triad that is critical in regulating bone remodeling, and also plays multiple roles in the immune system. OPG binds RANKL directly to block its interaction with RANK. In this article, we report the 2.7-A crystal structure of human RANKL trimer in complex with the N-terminal fragment of human OPG containing four cysteine-rich TNFR homologous domains (OPG-CRD). The structure shows that RANKL trimer uses three equivalent grooves between two neighboring monomers to interact with three OPG-CRD monomers symmetrically. A loop from the CRD3 domain of OPG-CRD inserts into the shallow groove of RANKL, providing the major binding determinant that is further confirmed by affinity measurement and osteoclast differentiation assay. These results, together with a previously reported mouse RANKL/RANK complex structure, reveal that OPG exerts its decoy receptor function ...
40 antibodies to RANKL (RANK Ligand) and validated for use in 10 applications (Immunohistochemistry, Western Blot, Flow Cytometry, Immunoprecipitation, ChIP assay, Immunocytochemistry, Blocking Assay, Functional Assay, ELISA, Neutralization)
Principal Investigator:KITAZAWA Riko, Project Period (FY):2002 - 2003, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Experimental pathology
Context: Prostate cancer (PCa) cells are characterised by an exquisite tropism for the bone, which translates into one of the highest rates of bone metastases and skeletal morbidity. New, effective treatments have emerged from a better understanding of the physiopathology of bone metastases. Objective: To summarise current insights and future perspectives in the therapy of PCa-induced bone disease. Evidence acquisition: This manuscript is based on presentations given at a satellite symposium held at the 2nd World Congress on Controversies in Urology (CURy) in Lisbon, Portugal. Data were retrieved from original and recent review papers on PCa-induced bone disease. Evidence synthesis: In normal, healthy bone, there is a balance between bone resorption and bone formation through the coordinated activity of osteoclasts and osteoblasts. The receptor activator of nuclear factor-kappa B ligand (RANKL) is an essential mediator of osteoclast formation, function, and survival. The RANKL pathway represents ...
Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is emerging as an important regulator of vascular pathophysiology. Here, we demonstrate a novel role of RANKL as a vascular permeability factor and a critical role of endothelial nitric oxide synthase (eNOS) in RANKL-induced endothelial function. RANKL increased the vascular permeability and leukocyte infiltration in vivo and caused the breakdown of the blood-retinal barrier in wild-type mice but not in eNOS-deficient mice. In vitro, it increased endothelial permeability and reduced VE-cadherin-facilitated endothelial cell-cell junctions in a NO-dependent manner. RANKL also led to the activation of Akt and eNOS and to NO production in endothelial cells (ECs). These effects were suppressed by the inhibition of TRAF6, phosphoinositide 3-kinase (PI3K), Akt, or NOS by genetic or pharmacologic means. Inhibition of the TRAF6-mediated NO pathway reduced EC migration and capillary-like tube formation in response to RANKL. Moreover, the ...
Sigma-Aldrich offers abstracts and full-text articles by [Gary J Spencer, Jennifer C Utting, Sharon L Etheridge, Timothy R Arnett, Paul G Genever].
Rabbit polyclonal RANKL antibody validated for WB, ELISA, IHC, ICC/IF and tested in Human. Referenced in 12 publications and 4 independent reviews.
购买RANKL兔多克隆抗体(ab65024),RANKL抗体经WB验证,可与人样本反应。5篇文献引用,产品出库一年都在质保范围内。中国现货速达。
Thirty-Four פודקאסטי Power Rank לשנת 2021. הפרק האחרון היה Dr. Eric Eager on predicting the NFL in 2021. האזינו אונליין, אין צורך בהרשמה.
TY - JOUR. T1 - Eriodictyol Inhibits RANKL-Induced Osteoclast Formation and Function Via Inhibition of NFATc1 Activity. AU - Song, Fangming. AU - Zhou, Lin. AU - Zhao, J.. AU - Liu, Q.. AU - Yang, Mingli. AU - Tan, R.. AU - Xu, J.. AU - Zhang, G.. AU - Quinn, J.M.W.. AU - Tickner, Jennifer. AU - Huang, Y.. AU - Xu, Jiake. PY - 2016/9. Y1 - 2016/9. N2 - © 2016 Wiley Periodicals, Inc. Receptor activator of nuclear factor kappa-B ligand (RANKL) induces differentiation and function of osteoclasts through triggering multiple signaling cascades, including NF-?B, MAPK, and Ca2+-dependent signals, which induce and activate critical transcription factor NFATc1. Targeting these signaling cascades may serve as an effective therapy against osteoclast-related diseases. Here, by screening a panel of natural plant extracts with known anti-inflammatory, anti-tumor, or anti-oxidant properties for possible anti-osteoclastogenic activities we identified Eriodictyol. This flavanone potently suppressed ...
Full Text - Excessive alcohol consumption is positively related to osteoporosis, and its treatment strategies are poorly developed. Disulfiram inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis; however, whether it can be used for ethanol-induced osteoclastogenesis and its underlying mechanism are still unclear. In this study, we demonstrated that ethanol promoted RANKL-induced osteoclast formation and bone resorption, whereas, disulfiram suppressed ethanol-induced osteoclastogenesis by abrogating the expression of nuclear factor of activated T cell c1 (NFATc1) in vitro. Further analysis revealed that aldehyde dehydrogenase 1A1 (ALDH1A1) is important for the expression of NFATc1, the master regulator of osteoclast differentiation. Furthermore, we showed that disulfiram protected ethanol-induced osteoporosis in vivo. Overall, our study provides promising evidence that disulfiram can be used as a treatment strategy for alcohol-related osteoporosis via the
The receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK)/osteoprotegerin (OPG) system is the final common pathway for bone resorption. Osteob... more
Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene. RANKL is known as a type II membrane protein and is a member of the tumor necrosis factor (TNF) superfamily. RANKL has been identified to affect the immune system and control bone regeneration and remodeling. RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls cell proliferation by modifying protein levels of Id4, Id2 and cyclin D1. RANKL is expressed in several tissues and organs including: skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas. Variation in concentration levels of RANKL throughout several organs, reconfirm ...
IL-1 is a proinflammatory cytokine that acts as an important mediator of the peripheral immune response during infection and inflammation (33). It is also known that IL-1 can induce bone destruction in a variety of diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease (34, 35). IL-1 stimulates osteoclast differentiation, fusion, and activation (35). In this paper, we examined the direct effect of IL-1 on osteoclast precursors which led to the elucidation of a previously unknown mechanism of downstream signaling pathways during IL-1-induced osteoclastogenesis.. Although TNF-α and IL-1 can activate early signaling pathways including NF-κB, JNK, and p38, which are important for RANKL-induced osteoclast differentiation, TNF-α alone has been shown to induce osteoclast differentiation in vitro (21, 36). IL-1 activates mature osteoclasts, thereby enhancing bone resorption (35), but our data along with previous studies (35, 36) demonstrate that IL-1 alone is insufficient to ...
IL-12, like IL-18, was shown to potently inhibit osteoclast formation in cultures of cocultures of murine osteoblast and spleen cells, as well as in adult spleen cells treated with M-CSF and receptor activator of NF-kappaB ligand (RANKL). Neither IL-12 nor IL-18 was able to inhibit RANKL-induced osteoclast formation in cultured RAW264.7 cells, demonstrating that IL-12, like IL-18, was unable to act directly on osteoclastic precursors. IL-12, like IL-18, was found to act by T cells, since depletion of T cells from the adult spleen cell cultures ablated the inhibitory action of IL-12 and addition of either CD4 or CD8 T cells from C57BL/6 mice to RANKL-stimulated RAW264.7 cultures permitted IL-12 or IL-18 to be inhibitory. Additionally, IL-12 was still able to inhibit osteoclast formation in cocultures with osteoblasts and spleen cells from either GM-CSF R(-/-) mice or IFN-gamma R(-/-) mice, indicating that neither GM-CSF nor IFN-gamma was mediating osteoclast inhibition in these cultures. Combined, IL-18
Based on our earlier observation that caspase-3 is present in osteoclasts that are not undergoing apoptosis, we investigated the role of this protein in the differentiation of primary osteoclasts and RAW264.7 cells (Szymczyk KH, et al, 2005, Caspase-3 activity is necessary for RANKL-induced osteoclast differentiation. The Proceedings of the 8th ICCBMT). We noted that osteoclast numbers are decreased in long bones of procaspase-3 knockout mice and that receptor activator of NF-κB ligand (RANKL) does not promote differentiation of isolated preosteoclasts. In addition, after treatment with inhibitors of caspase-3 activity, neither the wild-type primary nor the RAW264.7 cells express TRAP or became multinucleated. We found that immediately following RANKL treatment, procaspase-3 is cleaved and the activated protein is localized to lipid regions of the plasma membrane and the cytosol. We developed RAW264.7 procaspase-3 knockdown clonal cell lines using RNAi technology. Again, treatment with RANKL fails to
in Clinical & Experimental Immunology (2004), 138(3), 491-498. Crohns disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor ... [more ▼]. Crohns disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin (OPG) are potentially involved in this process as they regulate osteoclastogenesis and are influenced by pro-inflammatory cytokines. The aim of this study was to determine the levels of soluble RANKL (sRANKL), RANK and OPG expression both in the serum and in the colon of CD patients. Levels of sRANKL and OPG were assessed in the serum and the supernatants of cultured colonic biopsies in patients with CD and controls by ELISA. RANK expression was explored by immunostaining and immunofluorescence of fixed colonic samples. OPG and ...
Methods Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to be differentiated into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β, TG, or TAC. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the above effects of TAC on osteoclastogenesis were investigated by using RT-PCR and immunoblotting for osteoclast specific and ER stress signaling molecules, including PERK, IRE1, GRP78, eIF2α, c-Fos and NFATc1.. ...
Transforming growth factor beta (TGFbeta) is a multifunctional growth factor that is produced by many cells in bone and is abundant in the bone matrix. TGFbeta is known to regulate RANKL-induced osteoclast formation and bone resorbing activity. In this study we sought to determine whether TGFbeta could directly induce osteoclast formation by a RANKL-independent mechanism. We found that the addition of TGFbeta to cultures of human monocytes and RAW 264.7 cells (in the presence of M-CSF and the absence of RANKL, TNFalpha or IL-6/IL-11) was sufficient to induce the formation of TRAP+ and VNR+ cells, which formed actin rings and were capable of extensive lacunar resorption. The addition of osteoprotegerin or antibodies to TNFalpha and its receptors, as well as antibodies to gp130, did not inhibit lacunar resorption, indicating that TGFbeta did not act by stimulating RANKL, TNF or IL-6 production by monocytes. TGFbeta-induced osteoclast formation was qualitatively different from that induced by RANKL with
|i|Objective|/i|. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients.|i| Methods.|/i| Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed.|i| Results|/i|. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical |svg xmlns:xlink=http://www.w3.org/1999/xlink xmlns=http://www.w3.org/2000/svg style=
Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation. The expression levels of the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway were determined by Western blot analysis. To determine whether shikonin influences the receptor activator of nuclear factor-κB ligand (RANKL)-induced association between receptor activator of NF-κB (RANK) and tumor necrosis factor receptor associated factor 6 (TRAF6), immunofluorescence staining and immunoprecipitation experiments were performed. During our validation model, histomorphometric examination and micro-computed tomography (CT) were conducted to assess the morphology of osteoporosis.. ...
TY - JOUR. T1 - Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma. AU - Kim, Hyun Soo. AU - Yoon, Gun. AU - Do, Sung Im. AU - Kim, Sung Joo. AU - Kim, Youn Wha. PY - 2016/3/22. Y1 - 2016/3/22. N2 - A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and ...
A new inhibitor, placotylene A (1), of the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation, and a regioisomer of placotylene A, placotylene B (2), were isolated from a Korean marine sponge Placospongia sp. The chemical structures of placotylenes A and B were elucidated on the basis of 1D and 2D NMR, along with MS spectral analysis and revealed as an iodinated polyacetylene class of natural products. Placotylene A (1) displayed inhibitory activity against RANKL-induced osteoclast differentiation at 10 μM while placotylene B (2) did not show any significant activity up to 100 μM, respectively.
A small peptide, OP3-4, blocks receptor activator of NF-κB from binding to its ligand, receptor activator of NF-κB ligand (RANKL), and was reported recently to inhibit bone resorption, promote bone formation and protect cartilage in a preclinical rheumatoid arthritis model. The latter effects may result from inhibition of RANKL reverse signalling in osteoblasts and chondrocytes. Whether other RANKL inhibitors, such as denosumab, share this action is not known, but OP3-4 at least has potential to provide anabolic treatment for both systemic and focal bone loss in inflammatory arthritis.
Recent works demonstrated the difference of calcification genesis between carotid and femoral plaques, femoral plaques being more calcified. It has been clearly demonstrated that the molecular triad osteoprotegerin (OPG)/Receptor Activator of NFkB (RANK)/RANK Ligand (RANKL) exerts its activities in the osteoimmunology and vascular system. The aim of this study was to determine their expression and their potential role in calcifications of the atheromatous plaques located in two different peripheral arterial beds, carotid and femoral. The expression of OPG, RANK and RANKL was analyzed by immunochemistry in 40 carotid and femoral samples. Blood OPG and RANKL were quantified using specific ELISA assays. OPG staining was more frequently observed in carotid than in femoral plaques, especially in lipid core. Its expression correlated with macrophage infiltration more abundantly observed in carotid specimens. Surprisingly, serum OPG concentration was significantly lower in carotid population compared to
BACKGROUND: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly
2924 Genrally, prostatic cancer shows osteoblastic metastases, whereas the lesion also causes osteolysis. The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Using a reverse transcription-polymerase chain reaction approach, we investigated the effects of crude conditioned medium (CM) obtained from prostate cancer cell lines on mRNA level of receptor activator of NF-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) in mouse osteoblastic cell line, MC3T3-E1. Then we cocultured MC3T3-E1 with prostate cancer cell lines and evaluated mRNA level of RANKL and OPG in MC3T3-E1. Next, to investigate the effects on osteoclast precursor generated from mouse bone marrow treated with RANKL and MCSF, we cultured osteoclast precursor with crude CM obtained from prostate cancer cell lines in the presence or absence of RANKL or OPG. The number of multinucleated osteoclasts was evaluated by TRAP staining. Crude ...
The alternative or noncanonical nuclear factor kappa B (NF-κB) pathway regulates the osteoclast (OC) response to receptor activator of nuclear factor kappa B ligand (RANKL) and thus bone metabolism. Although several lines of evidence support the emerging concept that nucleotide-binding leucine-rich repeat and pyrin domain-containing receptor 12 (NLRP12) impedes alternative NF-κB activation in innate immune cells, a functional role for NLRP12 outside an inflammatory disease model has yet to be reported. Our study demonstrates that NLRP12 has a protective role in bone via suppression of alternative NF-κB-induced osteoclastogenesis and is down-modulated in response to osteoclastogenic stimuli. Here, we show that retroviral overexpression of NLRP12 suppressed RelB nuclear translocation and OC formation. Conversely, genetic ablation of NLRP12 promoted NIK stabilization, RelB nuclear translocation, and increased osteoclastogenesis in vitro. Using radiation chimeras, we demonstrated these in vitro ...
With the increasing age of people living with HIV/AIDS, age-induced osteoporosis is likely to be compounded by HIV/AIDS and HAART-associated bone loss. Mechanistically, osteoclasts the cells responsible for bone resorption form under the influence of the key osteoclastogenic cytokine Receptor- Activator of NF-KB (RANKL). The osteoclastogenic and proresorptive activities of RANKL are moderated by its physiological decoy receptor osteoprotegerin (OPG). Imbalance in the ratio of RANKL to OPG alters osteoclastic bone resorption and lead to osteoporosis. Activated T- and B-cells are a major source of RANKL, while normal physiological B-cells are a major source of OPG. T-cells regulate the production of OPG by B-cells. Thus changes in the immune system induced by HIV/AIDS and/or by HAART could affect B-cell and T-cells RANKL and OPG production. Indeed, data from our group shows that in an animal model of HIV/AIDS, the HIV-1 Transgenic rat, the development of osteoporosis is recapitulated as observed ...
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Hyaluronic acid (hyaluronan, HA) is a component of the extracellular matrix and is also used clinically to treat joint and cartilage diseases such as osteoarthritis. Chang et al. show that high molecular mass HA (HMM-HA), but not low molecular mass HA, inhibited osteoclast differentiation of bone marrow-derived macrophages in response to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). HMM-HA did not block RANKL-stimulated osteoclastogenesis of RAW264.7 cells, which is independent of M-CSF. Although CD44 is one known receptor for HA, antibodies that block CD44 had no effect on the inhibition of osteoclast formation by HA. However, function-blocking antibodies against Toll-like receptor 4 (TLR4) blocked the inhibitory effect of HA, suggesting that HA was acting through the TLR4. TLR4-transfected cells bound labeled HA based on fluorescence-activated cell sorting analysis, and osteoclastogenesis of cells from mice with a nonfunctional TLR4 ...
beta(3) integrin-null osteoclasts are dysfunctional, but their numbers are increased in vivo. In vitro, however, the number of beta(3)(-/-) osteoclasts is reduced because of arrested differentiation. This paradox suggests cytokine regulation of beta(3)(-/-) osteoclastogenesis differs in vitro and in vivo. In vitro, additional MCSF, but not receptor activator of NF-kappaB ligand (RANKL), completely rescues beta(3)(-/-) osteoclastogenesis. Similarly, activation of extracellular signal-regulated kinases (ERKs) and expression of c-Fos, both essential for osteoclastogenesis, are attenuated in beta(3)(-/-) preosteoclasts, but completely restored by additional MCSF. In fact, circulating and bone marrow cell membrane-bound MCSFs are enhanced in beta(3)(-/-) mice, correlating with the increase in the osteoclast number. To identify components of the MCSF receptor that is critical for osteoclastogenesis in beta(3)(-/-) cells, we retrovirally transduced authentic osteoclast precursors with chimeric c-Fms constructs
Bisphosphonates (BPs) have been commonly used in the treatment of osteolytic bone lesions, such as osteoporosis and osteogenesis imperfecta. However, serious side-effects can occur during the therapy. To search for novel potent BPs with lower side-effects, a series of imidazole-containing BPs (zoledronic acid [ZOL]; ZOL derivatives by substitution of the hydrogen at the 2-position on the imidazole ring with a methyl [MIDP], ethyl [EIDP], n-propyl [PIDP], or n-butyl group [BIDP]) were developed and the effects on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation were investigated using the murine macrophage RAW 264.7 cells at the protein, gene, and morphological and functional levels. Influences of these BPs on the cell growth and proliferation of RAW 264.7 were also studied in order to determine cytotoxicity. The results showed that PIDP significantly inhibited the RANKL-induced osteoclast formation in a dose-dependent fashion without inducing ...
Critical appraisal of denosumab in the treatment and prevention of postmenopausal osteoporosis and bone loss in patients undergoing hormone ablation David L Kendler1, Kenneth Shawn Davison21Prohealth Clinical Research, University of British Columbia, Vancouver, British Columbia, Canada; 2Department of Medicine, Division of Immunology and Rheumatology, Laval University, Quebec, CanadaAbstract: Antiresorptive therapies are the mainstay for treating patients with excessively high rates of bone resorption. The receptor activator of nuclear factor-κB (RANK) ligand (RANKL), secreted by osteoblasts, binds to the RANK receptor on the surface of preosteoclasts and osteoclasts to elicit osteoclast formation, survival, and activity. Osteoprotegerin, also secreted by the osteoblast, acts as a decoy RANK receptor reducing RANKL binding to RANK and reducing bone resorption. Denosumab, a fully human monoclonal antibody, has a high affinity and specificity for RANKL. Denosumab rapidly decreases bone resorption
Summary: Rapid progress has been made in recent years in our understanding of the mechanisms regulating the formation, activation, and survival of osteoclasts, which are derived from precursor cells in the myeloid lineage. In contrast, study of the regulation of osteoclast precursors (OCPs) has been relatively slow, in part because it has been hard to accurately identify them. However, following the discovery of cell-surface markers that facilitated purification of OCPs, recent studies have demonstrated that peripheral blood OCP numbers are increased in tumor necrosis factor (TNF)-mediated arthritis, both in animals and humans, and these numbers correlate with serum TNF levels. The increase can be reversed by anti-TNF therapy. Furthermore, the precursor cells that give rise to osteoclasts can also differentiate into other cell types, including dendritic cells. Receptor activator nuclear factor-κB ligand (RANKL) stimulates OCPs to produce pro-inflammatory cytokines and chemokines, and RANKL ...
Mature osteoclasts have an increased citric acid cycle and mitochondrial respiration to generate high ATP production and ultimately lead to bone resorption. However, changes in metabolic pathways during osteoclast differentiation have not been fully illustrated. We report that glycolysis and oxidative phosphorylation characterized by glucose and oxygen consumption as well as lactate production were increased during receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis from RAW264.7 and bone marrow-derived macrophage cells. Cell proliferation and differentiation varied according to glucose concentrations (0 to 100 mM). Maximal cell growth occurred at 20 mM glucose concentration and differentiation occurred at 5 mM concentration. Despite the similar growth rates exhibited when cultured cells were exposed to either 5 mM or 40 mM glucose, their differentiation was markedly decreased in high glucose concentrations. This finding suggests the possibility that ...
Receptor activator of NF-κB ligand (RANKL) activates, while osteoprotegerin (OPG) inhibits, osteoclastogenesis. A neutralizing Ab against RANKL, denosumab, improves bone strength in osteoporosis. OPG also improves muscle strength in mouse models of Duchennes muscular dystrophy (mdx) and denervation-induced atrophy, but its role and mechanisms of action on muscle weakness in other conditions remain to be investigated. We investigated the effects of RANKL inhibitors on muscle in osteoporotic women and mice that either overexpress RANKL (HuRANKLTg+), or lack Pparb and concomitantly develop sarcopenia (Pparb-/-). In women, taking denosumab for more than 3 years improved appendicular lean mass and handgrip strength compared with no treatment, whereas bisphosphonate did not. HuRANKLTg+ mice displayed lower limb force and maximal speed, while their leg muscle mass was diminished, with a lower number of type I and II fibers. Both OPG and denosumab increased limb force proportionally to the increase in ...
Osteoprotegerin (OPG) is membrane bound in the immune system but can also be produced and secreted almost everywhere in the organism, so that it is mainly available in soluble form. So far, the OPG/RANKL/RANK system has been most intensively studied in bone. The binding of RANKL on its receptor RANK, which is expressed by osteoclasts, activates a number of osteoclastic cell functions. OPG also has a key function in the vascular system. Patients with coronary heart disease (CAD) have elevated OPG serum levels, probably as a sign of ischemic or inflammatory endothelial damage. Elevated OPG levels were also found in patients with advanced heart failure, whereby OPG correlated with pro BNP (brain natriuretic peptide) and was a predictor for cardiovascular morbidity and mortality.. Our prospective cohort study will include 150 men (75 patients requiring surgery for CAD and a control group without coronary heart disease). The primary endpoints are the differences between the two groups in serum levels ...
353 Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calciumregulating hormones and bone turnover markers H Uemura, T Yasui, M Kiyokawa, A Kuwahara, H Ikawa, T Matsuzaki, M Maegawa, H Furumoto and M Irahara Department of Obstetrics and Gynecology, University of Tokushima, School of Medicine, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan (Requests for offprints should be addressed to H Uemura; Email: [email protected]) Abstract Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesisinhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during ...
Receptor Activator of NF-?B Ligand (RANKL) is a cell-bound marker (CD254) related to the TNF family of proteins. RANKL plays a critical role in bone metabolism, particularly osteoclast differentiation. In addition, RANKL is expressed by some T cells and i
Background In treating rheumatoid arthritis (RA), T2T (treat-to-Target) is the most reliable treatment strategy. Recent reports have indicated that reaching normal levels of bone mineral density (BMD) might be important for the prevention of fractures in osteoporosis treatment (reference 1 and 2).From this fact, there might be a possibility that T2T targeting BMD might be feasible also in osteoporosis treatment. In doing so, medicines with the ability to sufficiently increase BMD at a fast speed should be needed. Denosumab (DMAb) specifically inhibits the receptor activator for nuclear factor-kappa B ligand (RANKL) improves BMD rapidly at lumbar or hip. Therefore, DMAb is one of candidate drugs for T2T practice, and it is very important to know risk factors that attenuate its effect in the treatment of osteoporosis. ...
Osteoclasts, the only cells with bone tissue resorption functions through the usage of prostheses can inevitably result in the era of wear contaminants, the effective inhibition of osteoclast development, and bone tissue resorption could be a good way to avoid the loosening of prostheses and for that reason extend their lives. precursor cells in localized lesions in Varespladib RA. The overexpression of RANKL by energetic lymphocytes, macrophages, osteoblasts, etc. qualified prospects to extreme proliferation and irregular activation of osteoclasts due to the binding of RANKL to RANK on the top of osteoclast precursor cells and mature osteoclasts. As well as the overexpression of RANKL in broken joint bone tissue tissue, mRNA can be indicated by fibroblasts in the synovial cells, which leads towards the production from the RANKL proteins (36). Kotake et al. isolated multinucleated cells through the synovial lesions of RA individuals and demonstrated that they can form bone tissue absorption ...
TRAIL induced osteoclast differentiation is dependent on TRAF6.(A) Human peripheral blood mononuclear cells (PBMCs) were plated in 96-well plates at 1.5 × 105
Phenotypically different osteoclasts may be generated from different subsets of precursors. To what extent the formation of these osteoclasts is influenced or mediated by the inflammatory cytokine TNF-α, is unknown and was investigated in this study. The osteoclast precursors early blasts (CD31hi Ly-6C- ), myeloid blasts (CD31+ Ly-6C+ ), and monocytes (CD31- Ly-6Chi ) were sorted from mouse bone marrow using flow cytometry and cultured with M-CSF and RANKL, with or without TNF-α. Surprisingly, TNF-α prevented the differentiation of TRAcP+ osteoclasts generated from monocytes on plastic; an effect not seen with early blasts and myeloid blasts. This inhibitory effect could not be prevented by other cytokines such as IL-1β or IL-6. When monocytes were pre-cultured with M-CSF and RANKL followed by exposure to TNF-α, a stimulatory effect was found. TNF-α also stimulated monocytes osteoclastogenesis when the cells were seeded on bone. Gene expression analysis showed that when TNF-α was added to
Bone Metastasis-Free Survival. The median follow-up was 67.2 months in the denosumab group and 67.3 months in the placebo group. Median bone metastasis-free survival was not reached in either group (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.82-1.14, P = .70). Bone metastasis-free survival events occurred in 13% of the denosumab group vs 14% of the placebo group, including bone events in 7% vs 8%. Median disease-free survival was not reached in either group (HR = 1.04, P = .57). Disease-free survival events occurred in 20% vs 19% of patients.. Adverse Events. The most common grade ≥ 3 adverse events were neutropenia (15% vs 15%), febrile neutropenia (5% vs 6%), and leukopenia (3% vs 3%). Positively adjudicated osteonecrosis of the jaw occurred in 5% vs , 1% of patients. Atypical femur fracture occurred in nine patients (, 1%) vs no patients. Hypocalcemia of any grade occurred in 7% vs 4%.. The investigators concluded, Despite preclinical evidence suggesting RANKL inhibition ...
Robinson LJ, Yaroslavskiy BB, Griswold RD, Zadorozny EV, Guo L, Tourkova IL, Blair HC. Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-alpha with BCAR1 and Traf6. Exp Cell Res. 2009 Apr 15; 315(7):1287-301 ...
Osteoclasts;Estrogen;Postmenopause;Bone and Bones;Bone Remodeling;RANK Ligand;Carrier Proteins;Mutation;Osteoporosis, Postmenopausal;Osteoprotegerin;Glycoproteins;Receptor Activator of Nuclear Factor-kappa B;Receptors, Cytoplasmic and ...
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Abcams Osteoprotegerin ELISA Kit suitable for Cell culture supernatant, Serum, Plasma, Cell Lysate in human. Reliably quantify 1 pg/ml of Osteoprotegerin.
In the current study, we have generated a faithful computational model of the BMU. It is important to note that the homeostatic behavior is not hardcoded but emerges from the interactions between the different primary cell types of the bone in response to TGF-β, RANKL, and BDFs. Furthermore, informed by experimental evidence, the introduction of a simulated TGF-β ligand and receptor expressing prostate cancer cell into the BMU resulted in a vicious cycle that yielded mixed osteogenic/osteolytic lesions over clinically relevant periods of time. Key findings arising from the computational model include: (i) the ability to assess temporal changes in cellular populations and dissect complex dynamics that are difficult to determine in vivo, (ii) the phasic osteolytic/osteogenic nature of the metastases, (iii) the application of clinically used therapies such as bisphosphonates and anti-RANKL therapies illustrate the usefulness of the model in predicting the efficacy of targeted inhibitors, and (iv) ...
Receptor activator of NF-?B ligand (RANKL) is a TNF?-type cytokine that is produced by mesenchymal lineage cells such as chondrocytes, osteoblasts and osteocyte...
Use of an anti-IL-20 antibody, either alone or in combination with an anti-RANKL antibody, for treating breast cancer and inhibiting cancer-associated bone loss.
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Apoptosis, or programmed cell death, is a normal component of cellular differentiation and the development of multicellular organisms. Receptor activator ofNF-kB (RANK) lacks significant homology with the other family members of the tumor necrosis factor
Treatment with denosumab 60 mg and 180 mg (with background methotrexate) reduces the progression of bone erosion according to results of a 227 patient Phase II trial presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain.
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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 ...
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 ... 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 ... Precursors to osteoclasts, called pre-osteoclasts, express surface receptors called RANK (receptor activator of nuclear factor- ...
... 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 ...
Zoledronic acid (a bisphosphonate) and denosumab (a RANK-ligand-inhibitor) appear to be effective agents, but are associated ... Cochrane Urology Group) (December 2020). "Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone ... Elshan NG, Rettig MB, Jung ME (May 2019). "Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand ... All medications for CRPC block androgen receptor (AR) signaling via direct or indirect targeting of the AR ligand binding ...
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 ...
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 ...
Schoppet M, Preissner K, Hofbauer L (2002). "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and ... namely osteoprotegerin and RANK ligand. Note that these molecules also regulate differentiation of the osteoclast.[21] ... through RANK. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs and is not upregulated. ... which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK. It may be important to note that ...
"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 ...
The steric properties of phosphine ligands can be ranked by their steric properties. The Tolman cone angle is widely used.[10] ... 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 ... 1973). Transition Metal Complexes of Phosphorus, Arsenic, and Antimony Ligands. J. Wiley. ISBN 0-470-58117-4. .. . ...
... a novel mutation in TGFβ1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand. ...
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. ...
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 ...
... 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 ...
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 ...
The steric properties of phosphine ligands can be ranked by their Tolman cone angle. An important technique for the ... 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 ... interacting with metals as σ donor ligands. Phosphine ligands are also π-acceptors. Their π-acidity arises from overlap of P-C ...
In a treatment akin to the TEP analysis, the donor properties of N-heterocyclic carbene (NHC) ligands have been ranked ... If other ligands increase the density of π electrons on the metal, the C-O bond is weakened and ν(CO) decreases further; ... Carbonyl is a small ligand so steric factors do not complicate the analysis. Upon coordination of CO to a metal, ν(CO) ... This shift can be explained by π backbonding: the metal forms a π bond with the carbonyl ligand by donating electrons through ...
Ligands and metal ions can be ordered in many ways; one ranking system focuses on ligand 'hardness' (see also hard/soft acid/ ... field theory DNA binding ligand Inorganic chemistry Josiphos ligands Ligand dependent pathway Ligand field theory 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 ...
Fortune ranked Ligand as one of the top 100 fastest growing companies from 2014-2016 ranking as high as #6 in 2016. In 2014, ... "About :: Ligand Pharmaceuticals, Inc. (LGND)". Ligand. Retrieved 2018-09-12. "Ligand to Participate in Four Upcoming Investor ... Fortune ranked Ligand as among the top 100 fastest growing companies for 2014-2016, and in 2018 its CEO was listed among the ... In 2018, Van Doorn of MarketWatch ranked Ligand #2 on a list of the fastest-growing companies in the health-care sector. The ...
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 ...
... 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 ...
... "that the whole enterprise of ranking groups by degree of neoteny is fundamentally unjustified" (Gould, 1996, pg. 150).[21] Doug ...
Jung W, Krueger S, Renner C, Gause A, Sahin U, Trümper L, Pfreundschuh M (Dec 1994). "Opposite effects of the CD30 ligand are ...
A taxonomic rank or level of classification below kingdom and above class; in botany, the term division is commonly used in ... In this manner, effector molecules act as ligands that can increase or decrease enzyme activity, gene expression, or cell ... The basic unit of biological classification and the narrowest of the canonical taxonomic ranks, as well as a unit of ...
Using a ligand called Eind (1,1,3,3,5,5,7,7-octaethyl-s-hydrindacen-4-yl) germanium is able to form a double bond with oxygen ( ... Germanium ranks near fiftieth in relative abundance of the elements in the Earth's crust. In 1869, Dmitri Mendeleev predicted ...
4-1BB ligand • Kolesterilester transfer protein • Klasterin • Faktor stimulacije kolonije • Hemopeksin • Laktoferin • ...
Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.[6] ...
Allen TM (Oct 2002). "Ligand-targeted therapeutics in anticancer therapy". Nature Reviews. Cancer. 2 (10): 750-63. PMID ... found that patients receiving chemotherapy ranked nausea and vomiting as the first and second most severe side-effects, ... Active targeting uses biological molecules (antibodies, proteins, DNA and receptor ligands) to preferentially target the ...
... which in turn lead to the activation of RANK (a TNF receptor) protein that promote osteoclast formation. Oxidative stress ... signal-regulated kinase/signal transducer and activator of transcription 3/receptor activator of nuclear factor-kappaB ligand ...
Main article: Systematic evolution of ligands by exponential enrichment. in vitro selection[edit]. Because there are no known ... and so the exclusion of deoxyribozymes from the rank of "catalyst" simply because it does not feature multiple-turnover ... Deoxyribozymes should not be confused with DNA aptamers which are oligonucleotides that selectively bind a target ligand, but ...
Out of the 20 drugs ranked in order of individual and societal harm by David Nutt, LSD was third to last, or approximately 1/ ... the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand ... LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.[48] ...
Kuross SA, Rank BH, Hebbel RP (April 1988). "Excess heme in sickle erythrocyte inside-out membranes: possible role in thiol ... Dendritic cells, B-cells, and macrophages are equipped with special "co-stimulatory" ligands recognized by co-stimulatory ...
Simmons, J. G. (1996). The Scientific 100: A Ranking of the Most Influential Scientists, Past and Present. Carol. p. 19. ISBN ... even when the concentrations of inorganic ligands are much greater than those of organic ligands.[55] ... Tetramethylthorium, Th(CH3)4, is not known, but its adducts are stabilised by phosphine ligands.[34] ... Th4+ favours hard ligands with oxygen atoms as donors: complexes with sulfur atoms as donors are less stable and are more prone ...
The ligand of this receptor is macrophage inflammatory protein 3 alpha (MIP-3 alpha). This receptor has been shown to be ... 2002). "Human B cells become highly responsive to macrophage-inflammatory protein-3 alpha/CC chemokine ligand-20 after cellular ... ligand binding, and signaling". Biochemistry. 41 (26): 8332-41. doi:10.1021/bi025855y. PMID 12081481.. ... activation without changes in CCR6 expression or ligand binding". J. Immunol. 168 (10): 4871-80. doi:10.4049/jimmunol.168.10. ...
4-1BB ligand • Faktor aktivacije B-ćelija • FAS ligand • Limfotoksin • OX40L • RANKL • TRAIL ... http://www.clinicaltrials.gov/ct2/show/NCT00420212?term=biogen&recr=Open&rank=12. pristupljeno 12. 11. 2007.. ... "http://www.clinicaltrial.gov/ct2/show/NCT00213135?term=clarity&rank=3 clinicaltrial.gov. ...
2003). Neuroimaging techniques, like PET, were used in combination with a 5-HTT ligand in human ecstasy users, showing lower ... from 1991 to 1996 the Top 100 poll were ranked by the magazine's journalists; in 1997 the poll became a public vote. The ...
Type I IFN receptor forms a ternary complex, composed of its two subunits IFNAR1 and IFNAR2, and a type I IFN ligand. Ligand ... ligand-induced changes to internalization and trafficking of the receptor[8] and currently unappreciated differences to ligand- ... Each subunit of IFNAR contains an N-terminal ligand binding domain (with two or four fibronectin type II-like subdomains, for ... Structural analysis of type I IFN receptor with different type I IFN ligand subtypes revealed a similar binding site for the ...
Werner noted only two isomers (fac- and mer-) of the complex [CrCl3(NH3)3] could be formed, and concluded the ligands must be ... Cheung, A. C.; Rank, D. M.; Townes, C. H.; Thornton, D. D.; Welch, W. J. (1968). "Detection of NH3 molecules in the ... Ammonia can act as a ligand in transition metal complexes. It is a pure σ-donor, in the middle of the spectrochemical series, ... An ammine ligand bound to a metal ion is markedly more acidic than a free ammonia molecule, although deprotonation in aqueous ...
... 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 ... There is a hereditary factor in the development of Paget's disease of bone.[17][18] Two genes, SQSTM1 and RANK, and specific ... Whyte MP (2006). "Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling". Annals of the New York ...
For elution, an excess amount of a compound able to act as a metal ion ligand, such as imidazole, is used. GST has an affinity ... The affinity measure and ranking of affinity can be achieved by processing the obtained retention times of analyzed compounds. ... Dye ligand media is nonspecific, but mimics biological substrates and proteins. Glutathione is useful for separation of GST ... The ligands used in affinity chromatography are obtained from both organic and inorganic sources. Examples of biological ...
Ligand. ]. [. Receptor. ]. [. Complex. ]. Δ. G. bind. =. Δ. G. desolvation. +. Δ. G. motion. +. Δ. G. configuration. +. Δ. G. ... Rajamani R, Good AC (May 2007). "Ranking poses in structure-based lead discovery and optimization: current trends in scoring ... Ligand-basedEdit. Ligand-based drug design (or indirect drug design) relies on knowledge of other molecules that bind to the ... A second category is de novo design of new ligands. In this method, ligand molecules are built up within the constraints of the ...
... preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased ... receptor ligand activity. • peptide hormone receptor binding. • RNA polymerase II transcription factor activity, sequence- ... Coetzee M, Kruger MC (May 2004). "Osteoprotegerin-receptor activator of nuclear factor-kappaB ligand ratio: a new approach to ... Savvides SN, Boone T, Andrew Karplus P (Jun 2000). "Flt3 ligand structure and unexpected commonalities of helical bundles and ...
In humans, the biological roles of zinc are ubiquitous.[9][164] It interacts with "a wide range of organic ligands",[9] and has ... Rank. Country. Tonnes 1. China. 5,000,000 2. Australia. 1,500,000 3. Peru. 1,300,000 ... Zinc(I) compounds are rare and need bulky ligands to stabilize the low oxidation state. Most zinc(I) compounds contain formally ... with zinc chloride forms diphenylzinc that continues to react in an asymmetric reaction first with the MIB ligand and then with ...
IFNγ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, ... positive regulation of tumor necrosis factor (ligand) superfamily member 11 production. • positive regulation of interleukin-12 ...
TNFRSF10A (CD261) • TNFRSF10B (CD262) • TNFRSF10C (CD263) • TNFRSF10D (CD264) • TNFRSF11A (CD265/RANK) • TNFRSF11B ( ... On sadrži ligand-vezujući domen. Nakon vezivanja glutamata za mGluR receptor, N-terminalni rep podleže konformacionoj promeni ... Sedam transmembranskih heliksa formira šupljinu unutar ćelijske membrane koja služi kao ligand-vezujući domen, koji je često ... Pošto ta petlja sačinjava „poklopac" koji pokriva vrh ligand vezujućeg mesta, ova konformaciona razlika je dobra ilustracija ...
By examining the structure of these variable regions with different ligands bound (such as the MMDB) one can see which residues ... rank. DQ2 α5-β2. 2.5 05:01♣. 02:01 13. 16 2nd. ...
... ligands) in liquids. Solubility will also depend on the excess or deficiency of a common ion in the solution, a phenomenon ... The logarithm of these two values enables compounds to be ranked in terms of hydrophilicity (or hydrophobicity). ... and protein ligand binding. Aqueous solubility is of fundamental interest owing to the vital biological and transportation ...
"Rank order of vitamin A content in foods per 100 g". USDA National Nutrient Database. 29 March 2017. Retrieved 26 April 2017.. ... due to its activity as a ligand for nuclear receptors.[16] The physiological form of retinoic acid (all-trans-retinoic acid) ... These combined interventions were ranked by the Copenhagen Consensus 2008 as the world's best development investment.[28] ...
Osteoprotegerin and rank ligand expression in prostate cancer.. Brown JM1, Corey E, Lee ZD, True LD, Yun TJ, Tondravi M, ... To investigate the expression of osteoprotegerin (OPG) and RANK ligand (RANKL) in human prostatic tissues. The factors ...
NHS Evidence on RANK ligand Centre for Reviews and Dissemination databases -DARE & NHS EED (evaluates reliability of research) ... Tumor necrosis factor ligand superfamily member 11, receptor activator of nuclear factor kappa B ligand, TNF-related activation ... Receptor activator of nuclear factor-κB ligand is an osteoclast differentiation and activation factor which also augments the ... Chemical Information on RANK ligand. Protein Structural Information on RANK ligand. Biological Information (GenomeNet) on RANK ...
Nonstandard abbreviations used: receptor activator of NF-κB (RANK); RANK ligand (RANKL); marrow stromal cells (MSCs); ... Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. Guitty Eghbali-Fatourechi,1 Sundeep ... Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism c-Jun repression. ... TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J. Clin. ...
"RANK Ligand" by people in Harvard Catalyst Profiles by year, and whether "RANK Ligand" was a major or minor topic of these ... "RANK Ligand" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Below are the most recent publications written about "RANK Ligand" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "RANK Ligand". ...
RANK Ligand) Mouse anti-Human, Mouse, Rat, Clone: 12A668, Invitrogen 100 µg; Unconjugated. ... ligand} has been implicated in interactions between T cells and dendritic cells. RANK ligand (RANKL/TRANCE) binds to RANK on ... As OPGL/ODF (Osteoprotegerin Ligand/Osteoclast differentiation factor), the same protein can both activate mature osteoclasts ... TRANCE (TNF-related activation-induced cytokine receptor) or RANKL {receptor activator of NF-kB (RANK) ...
RANK Ligand) and validated for use in 10 applications (Immunohistochemistry, Western Blot, Flow Cytometry, Immunoprecipitation ... RANK Ligand). Find the RANKL (RANK Ligand) antibody that fits your needs. Choose from 1 of 40 RANKL (RANK Ligand) antibodies, ... CD254; H-RANK-L; M-Rank-L; ODF; OPG ligand; OPGL; Osteoclast differentiation factor; Osteoprotegerin ligand; rank-l; RANKL; ... RANKL (RANK Ligand) Antibodies Antibodies that detect RANKL (RANK Ligand) can be used in several scientific applications, ...
RANK Ligand) Monoclonal (MIH24), eBioscience™, Catalog # 12-6619-82. Tested in Flow Cytometry (Flow) applications. This ... Protein Aliases: CD254; H-RANK-L; M-Rank-L; ODF; OPGL; Osteoclast differentiation factor; Osteoprotegerin ligand; rank-l; RANKL ... RANK Ligand) Monoclonal Antibody (MIH24), PE, eBioscience™. The following product was used in this experiment: CD254 (RANK ... tumor necrosis factor ligand 6B; Tumor necrosis factor ligand superfamily member 11; Tumor necrosis factor ligand superfamily ...
It binds to RANK on cells of the myeloid lineage and functions as a key factor for osteoclast differentiation and activation. ... cells of the osteoblast lineage and it is a potent inhibitor of osteoclast formation by preventing the binding of RANKL to RANK ... About RANK Ligand:. RANKL aka RANK Ligand is receptor activator of nuclear factor kappa-Β ligand and also known as tumour ... RANKL is a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK, an apoptosis regulator gene and controls ...
The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-κβ ligand (RANKL) and ... Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthritis: observations from a proof-of- ... Crotti TN, Smith MD, Weedon H, Ahern MJ, Findlay DM, Kraan M et al (2002) Receptor activator NF-kappaB ligand (RANKL) ... The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-κβ ligand (RANKL) and ...
Rank Ligand Inhibitors. Chapter 5. Global Osteoporosis Treatment Market, by Geography, 2015 - 2025 (US$ Mn). Chapter 6. Company ... Global Osteoporosis Treatment Market 2017-2025: Bisphosphonates, Parathyroid Hormone Therapy, Calcitonin, SERM and Rank Ligand ... and rank ligand inhibitors. Bisphosphonates is extensively used for prevention and treatment of osteoporosis, thus dominating ...
RANK ligand answers are found in the Tabers Medical Dictionary powered by Unbound Medicine. Available for iPhone, iPad, ... RANKL, RANK ligand is a topic covered in the Tabers Medical Dictionary. To view the entire topic, please sign in or purchase a ... "RANKL, RANK Ligand." Tabers Medical Dictionary, 23rd ed., F.A. Davis Company, 2017. Tabers Online, www.tabers.com/ ... tabersonline/view/Tabers-Dictionary/746725/all/RANKL__RANK_ligand. RANKL, RANK ligand. In: Venes D, ed. Tabers Medical ...
Receptor Activator of NF-κB Ligand (RANKL) is a cell-bound marker (CD254) related to the TNF family of proteins. RANKL plays a ... Tumor necrosis factor ligand superfamily member 11, Receptor activator of nuclear factor kappa-B ligand, RANKL, CD254, ... Receptor Activator of NF-κB Ligand (RANKL) is a cell-bound marker (CD254) related to the TNF family of proteins. RANKL plays a ...
RANK Ligand) is a cell-bound marker (CD254) related to the TNF family of proteins. RANK Ligand plays a critical role in bone ... Receptor Activator of NF-κB Ligand (RANK Ligand) is a cell-bound marker (CD254) related to the TNF family of proteins. RANK ... In addition, RANK Ligand is expressed by some T cells is a dendritic cell survival factor and is involved in the regulation of ... Tumor necrosis factor ligand superfamily member 11, Receptor activator of nuclear factor kappa-B ligand, RANKL, CD254, ...
RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic ... RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic ... RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic ... RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic ...
RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway (Homo sapiens). From WikiPathways. Revision as of 18:16, 23 ... RANKL/RANK Signaling Pathway. Osteoclastogenesis. RAC1. NFKB1. LYN. MAP2K1. FHL2. MITF. SYK. MAP2K6. GTP. 29, 67. P. 17, 35, 54 ... It binds to Receptor activator of NF-kB (RANK) and plays a major role in the regulation of osteoclast function. Binding of ... Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor necrosis factor (TNF) superfamily. ...
RANKL/RANK Signaling Pathway. SYK. FHL2. LYN. RAC1. MAP2K6. NFKB1. MAP2K1. MITF. P. GTP. P. TNFRSF11B. MAP2K7. TRAF6. Ub. ... RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway (Homo sapiens). From WikiPathways. Revision as of 06:04, 1 ... RANKL (Receptor activator of nuclear factor-kappa B ligand), RANK (Receptor activator of nuclear factor-kappa B) and the ... Ligand. Receptor. Protein. Protein - protein dissociation. Enzyme Complex. Small molecule. Induced activation. Inhibition. Auto ...
Ranking ligand affinity for the DNA minor groove by experiment and simulation ... Ranking ligand affinity for the DNA minor groove by experiment and simulation. Medicinal Chemistry Letters, 1 (8). pp. 376-680 ... these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand ... ligand affinity, DNA minor groove, minor groove binders, DNA footprinting, NMR spectroscopy, isothermal titration calorimetry, ...
Ranking docking poses by graph matching of protein-ligand interactions: lessons learned from the D3R Grand Challenge 2. ... Although the obtained ranking is still unsuitable for hit to lead optimization, the GRIM-HYDE scoring scheme is accurate and ... GRIM aligns protein-ligand interaction patterns of docked poses to those of available PDB templates for the target protein, and ... A novel docking challenge has been set by the Drug Design Data Resource (D3R) in order to predict the pose and affinity ranking ...
Download Free Full-Text of an article EFFECT OF THE RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KB AND RANK LIGAND ONIN VITRO ... EFFECT OF THE RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KB AND RANK LIGAND ONIN VITRO DIFFERENTIATION OF CORD BLOOD CD133+ ... Keyword(s): RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B, RANK LIGAND, HEMATOPOIETIC STEM CELLS, OSTEOCLASTS, CALCITONIN ... Some studies demonstrated that U-266 myeloma cell line and primary myeloma cells expressed RANK and RANKL. It had been reported ...
Title:Combining docking pose rank and structure with deep learning improves protein-ligand binding mode prediction. Authors: ... This network division allows contributions from ligand identity to be distinguished from effects of protein-ligand interactions ... We develop a deep learning model for binding mode prediction that uses docking ranking as input in combination with docking ... and fed into a dual-graph architecture that includes separate sub-networks for the ligand bonded topology and the ligand- ...
... soluble stands for receptor activator of NF-κB ligand, soluble. Human RANK-Ligand - soluble is a recombinant protein optimized ... RANK-Ligand - soluble stands for receptor activator of NF-κB ligand, soluble. Human RANK-Ligand - soluble is a recombinant ... High expression of RANK-Ligand is observed during degenerative bone diseases and in tumors. Human RANK-Ligand shares with mouse ... Receptor activator of nuclear factor kappa-B (RANK) ligand, also known as tumor necrosis factor ligand superfamily member 11 ( ...
Mouse RANK-Ligand is a recombinant protein optimized for use in cell culture, differentiation studies, and functional assays. ... RANK-Ligand stands for receptor activator of NF-κB ligand, also termed TNSFSF11 or TRANCE. ... RANK-Ligand stands for receptor activator of NF-κB ligand, also termed TNSFSF11 or TRANCE. Mouse RANK-Ligand is a recombinant ... High expression of RANK-Ligand is observed during degenerative bone diseases and in tumors. Mouse RANK-Ligand shares with human ...
Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL) and Mammographic Density in Premenopausal Women ... Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL) and Mammographic Density in Premenopausal Women ... Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL) and Mammographic Density in Premenopausal Women ... Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL) and Mammographic Density in Premenopausal Women ...
We, therefore, investigated the associations of circulating RANK and soluble RANK ligand (sRANKL) with mammographic density in ... Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal ... Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal ... Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal ...
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RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Title. RANK ligand as a potential ... RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers ...
RANK Ligand plays a critical role in bone metabolism and osteoclast differentiation. T cell expression of RANK Ligand promotes ... RANK Ligand) is a cell-bound marker related to the tumor necrosis factor (TNF) family of proteins. ... Receptor activator of nuclear factor kappa-B Ligand ( ... Mouse RANK Ligand. Receptor activator of nuclear factor kappa-B ... RANK Ligand plays a critical role in bone metabolism and osteoclast differentiation. T cell expression of RANK Ligand promotes ...
Basically in the ranking performance evaluation, we keep a grand-truth ranking list which is the molecule ranking for a given ... The list-wise approach takes ranking lists of objects as instances in learning and learns the ranking model based on ranking ... is ideal ranking and ŷ is the predicted ranking, for the top-k in the predicted ranking list, NDCG [8] is calculated as ... In the training procedure, the aim of LOR is to train a local ranking model f(T, C) = f(x) that can assign a ranking score to a ...
RANK-Ligand Inhibitor. Side effects: Possible skin changes like rashes and eczema and a small increased risk of infection ...
  • As OPGL/ODF (Osteoprotegerin Ligand/Osteoclast differentiation factor), the same protein can both activate mature osteoclasts and mediate osteoclastogenesis. (fishersci.com)
  • Description: The MIH24 monoclonal antibody reacts with human TRANCE (TNF-related activation-induced cytokine receptor) also known as RANKL (receptor activator of NF-kappaB ligand) and OPGL (Osteoprotegerin Ligand). (thermofisher.com)
  • RANKL aka RANK Ligand is receptor activator of nuclear factor kappa-Β ligand and also known as tumour necrosis factor ligand superfamily member 11 (TNFSF11), osteoclast differentiation factor (ODF), TNF-related activation-induced cytokine (TRANCE) and osteoprotegerin ligand (OPGL). (prospecbio.com)
  • Osteoprotegerin-ligand (OPGL) is a key osteoclast differentiation/activation factor essential for bone remodeling. (nih.gov)
  • Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. (duke.edu)
  • 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. (duke.edu)
  • The global osteoporosis treatment market is segmented by drug type into bisphosphonates, parathyroid hormone therapy, calcitonin, selective estrogen inhibitors modulator (SERM) and rank ligand inhibitors. (prnewswire.co.uk)
  • Per this agreement, Ligand will apply Vernalis Design Platform ("VDP") for designing small molecule inhibitors for the undisclosed oncology target. (nasdaq.com)
  • Denosumab injection (Xgeva) is used Denosumab injection is in a class of medications called RANK ligand inhibitors. (medlineplus.gov)
  • The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. (ru.nl)
  • This systematic review assessed the effects of (1) radiotherapy, (2) radiotherapy combined with bisphosphonates, and (3) radiotherapy combined with RANK ligand (RANKL) inhibitors on bone quality and bone strength in bone metastases originating from solid tumors. (ru.nl)
  • Recently, RANK [receptor activator of nuclear factor kappa-B] ligand inhibitors, such as denosumab, which has an effect on bone, have been developed. (medscape.com)
  • Should we consider looking at drugs like abiraterone, using the RANK ligand inhibitors and chemotherapy? (medscape.com)
  • Genetic experiments have shown that mice lacking either rankl or rank suffer from severe osteoporosis and defective tooth eruption due to complete lack of osteoclasts. (wikipathways.org)
  • Binding of RANKL to RANK triggers downstream signaling events that leads to the activation of osteoclasts and controlling of lineage commitment. (wikipathways.org)
  • The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. (duke.edu)
  • Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. (duke.edu)
  • RANK Ligand-driven osteoclast activity osteoclasts being those cells which erode the bones has been implicated in the destructive bone erosions which are characteristic of rheumatoid arthritis and other forms of erosive arthritis such as psoriatic arthritis. (healthcentral.com)
  • The generation of osteoclasts depends on RANK Ligand. (healthcentral.com)
  • The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. (frontiersin.org)
  • The significance of RANK-RANKL pathway is supported by studies that show that disruption in either rank or rankl in mice produced severe osteopetrosis and defective tooth eruption resulting from a complete lack of osteoclasts ( 6 ). (aacrjournals.org)
  • RANKL binds to RANK expressed by osteoclasts and osteoclast precursors to promote osteoclast differentiation. (medscape.com)
  • Pre-osteoclasts have membrane receptors called RANK, related to the TNF family. (washington.edu)
  • When RANK-L activates these receptors the cells fuse and differentiate into mature multinucleared osteoclasts which develop a ruffled border and resorb bone. (washington.edu)
  • Osteoclasts are regulated by the RANK ligand pathway. (aacrjournals.org)
  • 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. (curehunter.com)
  • Pre-osteoclasts are activated by RANK-ligand (RANKL) and then differentiate into mature osteoclasts which develop a ruffled border and resorb bone. (dentalcare.com)
  • Osteoclasts are more effective at resorbing bone when RANK-ligand's effect is reduced. (dentalcare.com)
  • Osteoclastic activity is triggered via the osteoblasts' surface-bound RANKL activating the osteoclasts' surface-bound receptor activator of nuclear factor kappa-B (RANK). (wikipedia.org)
  • The following product was used in this experiment: CD254 (RANK Ligand) Monoclonal Antibody (MIH24), PE, eBioscience™ from Thermo Fisher Scientific, catalog # 12-6619-82, RRID AB_466137. (thermofisher.com)
  • Receptor Activator of NF-κB Ligand (RANKL) is a cell-bound marker (CD254) related to the TNF family of proteins. (cellsciences.com)
  • Traditional treatment strategies include analgesics, external beam radiation therapy (EBRT), and bone acting agents such as bisphosphonates or the receptor activator of nuclear factor kappa-B ligand (RANKL) monoclonal antibody denosumab. (hindawi.com)
  • Denosumab is a monoclonal antibody which targets RANK Ligand, a cell mediator that break down bone. (healthcentral.com)
  • Denosumab is a RANK ligand (RANKL) inhibitor/human monoclonal antibody. (nof.org)
  • We report that mice lacking OPGL or its receptor RANK fail to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. (nih.gov)
  • Transplantation and OPGL-rescue experiments in opgl-/- and rank-/- pregnant females showed that OPGL acts directly on RANK-expressing mammary epithelial cells. (nih.gov)
  • Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. (duke.edu)
  • Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. (duke.edu)
  • 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. (duke.edu)
  • These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells. (duke.edu)
  • Receptor activator of nuclear factor-κB ligand is an osteoclast differentiation and activation factor which also augments the ability of dendritic cells to cause T-cell proliferation. (ganfyd.org)
  • The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-κβ ligand (RANKL) and osteoprotegerin (OPG) as biomarkers of disease activity, progressive joint damage, and therapeutic response, during cytokine blockade in rheumatoid arthritis (RA). (springer.com)
  • Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor necrosis factor (TNF) superfamily. (wikipathways.org)
  • RANKL (Receptor activator of nuclear factor-kappa B ligand), RANK (Receptor activator of nuclear factor-kappa B) and the natural decoy receptor of RANKL, OPG (Osteoprotegerin) are three important molecules identified to play a major role in osteoclastogenesis and bone remodelling. (wikipathways.org)
  • Objective: Receptor activator of nuclear factor-kappa B ligand (RANKL) appears to be an osteoclast-activating factor, bearing an important role in the pathogenesis of multiple myeloma. (sid.ir)
  • Receptor activator of nuclear factor kappa-B (RANK) ligand, also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), together with RANK, is a member of the TNF superfamily of ligands and receptors involved in activation of immune response and in bone regeneration. (miltenyibiotec.com)
  • The receptor activator of nuclear factor-κB (RANK) pathway plays essential roles in breast development. (aacrjournals.org)
  • Receptor activator of nuclear factor kappa-B Ligand (RANK Ligand) is a cell-bound marker related to the tumor necrosis factor (TNF) family of proteins. (shenandoah-bt.com)
  • At non-cytotoxic concentrations, AaE and active components, artemisinin, artemisinic acid, and arteannuin B, potently inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis and the formation of osteoclast-mediated resorption pits. (nih.gov)
  • Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. (biomedcentral.com)
  • receptor activator of nuclear factor kappa-B (RANK), its ligand (RANKL), and osteoprotegerin (OPG). (biomedcentral.com)
  • [10] Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor) . (wikipedia.org)
  • Receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) has emerged as a major mediator of bone resorption, commonly associated with cancer and other chronic inflammatory diseases. (aacrjournals.org)
  • What is the role of receptor activator of nuclear factor-kappa B ligand (RANKL) and receptor activator of nuclear factor-kappa B (RANK) in the pathogenesis of osteoporosis? (medscape.com)
  • The receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK)/osteoprotegerin (OPG) system is the final common pathway for bone resorption. (medscape.com)
  • RANKL is specifically categorized under the TNFSF11, the TNF ligand superfamily member. (wikipedia.org)
  • Ligand Pharmaceuticals Incorporated LGND announced that its subsidiary, Vernalis has signed a research collaboration agreement with privately-held PhoreMost Limited for an undisclosed novel oncology target. (nasdaq.com)
  • Why Is Ligand (LGND) Up 5.3% Since Last Earnings Report? (benzinga.com)
  • Ligand Pharmaceuticals Incorporated (NASDAQ:LGND) (the Company or Ligand) today announced that the United States Patent and Trademark Office issued U.S. Patent No. 7,314,887, titled "Thrombopoietin Activity Modulating Compounds and Methods," to Ligand for LGD-4665, the Company's lead thrombopoietin (TPO) receptor agonist and a family of related compounds. (ligand.com)
  • RANKL/RANK signaling is essential for skeletal homoeostasis and its interference leads to inhibition of bone resorption resulting in bone diseases including osteoporosis osteopetrosis and rheumatoid arthritis. (wikipathways.org)
  • The receptor activator of NFκB ligand (RANKL) is a critical mediator of osteoclastogenesis and regulates cathepsin K (CTSK) expression, which is essential for normal bone resorption. (elsevier.com)
  • a ) the RANK ligand/osteoprotegerin pathway, which regulates osteoclast formation and bone resorption, ( b ) the Runx2 transcription factor, which controls osteoblast differentiation, and ( c ) the Wnt signaling pathway, which regulates osteoblasts and bone formation. (aacrjournals.org)
  • The investigators' data suggests that PSA may contribute to the high bone resorption seen in prostate cancer by increasing the ratio of RANK ligand (increased by PSA) to osteoprotegerin (decreased 95× by PSA). (aacrjournals.org)
  • This network division allows contributions from ligand identity to be distinguished from effects of protein-ligand interactions on classification. (arxiv.org)
  • RANKL can also bind to osteoprotegerin, a protein secreted mainly by cells of the osteoblast lineage and it is a potent inhibitor of osteoclast formation by preventing the binding of RANKL to RANK. (prospecbio.com)
  • These plots are of VM2 calculated binding free energy predictions versus experimental binding affinities for the protein receptors P38A kinase, HIV-1 protease, PDE10A, and BRCA1, and corresponding inhibitor series ranging between 16 and 38 ligands. (verachem.com)
  • Although best known for their important antibody-producing capabilities, B cells also produce two cytokines critical for bone metabolism: the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) and its physiological inhibitor osteoprotegerin (OPG). (frontiersin.org)
  • In contrast, genetic deletion of osteoprotegerin, a decoy receptor for RANKL and an inhibitor of RANK, produced osteoporosis resulting from an increased number of osteoclast ( 7 ). (aacrjournals.org)
  • Osteoprotegerin (OPG), The Endogenous Inhibitor of Receptor Activator of NF-κB Ligand (RANKL), is Dysregulated in BRCA Mutation Carriers. (nih.gov)
  • Binding of RANKL to RANK leads to the activation of signaling modules such as NF-kappa B, mitogen activated protein kinases (MAPK's), protein kinase C (PKC), Ca2+/Calcineurin/nuclear factor of activated T cells (NFAT) and phosphatidyl 3-kinase (PI3K). (wikipathways.org)
  • TRANCE (TNF-related activation-induced cytokine receptor) or RANKL {receptor activator of NF-kB (RANK) ligand} has been implicated in interactions between T cells and dendritic cells. (fishersci.com)
  • Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors. (harvard.edu)
  • Integrins are cell-surface receptors that bind ligands and reduce their bone-building effect. (dentalcare.com)
  • The RANKL-RANK signaling system is negatively regulated by a decoy receptor known as Osteoprotegerin. (wikipathways.org)
  • OPG is the decoy receptor for RANKL and can downregulate RANK-signaling. (biomedcentral.com)
  • OPG is a soluble decoy receptor that inhibits RANK-RANKL by binding and sequestering RANKL. (medscape.com)
  • Meanwhile, OPG is a free-floating decoy receptor, made by mature osteoblasts, which can bind the RANK-L. (washington.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. (thermofisher.com)
  • RANK ligand and osteoprotegerin are members of the tumor necrosis factor ligand and receptor superfamilies with opposing actions to stimulate osteoclast formation, activity, and survival ( 8 ). (aacrjournals.org)
  • The Patent Scorecard--Quarterly Leader Board report, issued on 11/30/2007, listed Ligand Pharmaceuticals Incorporated as one of the top innovators in the industry with the highest score for the Industry Impact metric ( www.patentboard.com/scorecard ). (ligand.com)
  • No impact of anti-Rank ligand and PTH analogs on cardiovascular risk in postmenopausal osteoporosis: a systematic literature review and meta-analysis. (bvsalud.org)
  • The anti- Rank ligand and PTH analogs have no impact on cardiovascular risk and overall mortality in idiopathic osteoporosis . (bvsalud.org)
  • Lee C, Baek JM, Kim JY, Lee WS, Yoo WH, Lee MS. Ebselen Is a Potential Anti-Osteoporosis Agent By Suppressing RANK Ligand-Induced Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Inflammatory Bone Destruction In Vivo [abstract]. (acrabstracts.org)
  • Ligand discovers and develops new drugs that address critical unmet medical needs of patients in the areas of thrombocytopenia, hepatitis C, cancer, hormone-related diseases, osteoporosis and inflammatory diseases. (ligand.com)
  • Catalytic subunits, IκB kinase α and IκB kinase β and the non-catalytic subunit IKKγ (also called NEMO) are also essential for RANKL-RANK signaling and osteoclastogenesis. (wikipathways.org)
  • Binding of osteoprotegerin (OPG) by RANK-Ligand inhibits osteoclastogenesis and leads to accumulation of bone and cartilage. (miltenyibiotec.com)
  • Since then, using DNA footprinting, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and molecular dynamics, we have established that the flanking bases around the central 4 being read by the ligand have subtle effects on recognition. (strath.ac.uk)
  • RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1) through RANK . (wikipedia.org)
  • It binds to RANK on cells of the myeloid lineage and functions as a key factor for osteoclast differentiation and activation. (prospecbio.com)
  • A comprehensive manually curated reaction map of RANKL/RANK signaling pathway. (wikipathways.org)
  • RANK ligand (RANKL/TRANCE) binds to RANK on dendritic cells, upregulates the expression of anti-apoptotic protein BcL-XL suggesting a role in dendritic cell survival. (fishersci.com)
  • It binds to Receptor activator of NF-kB (RANK) and plays a major role in the regulation of osteoclast function. (wikipathways.org)
  • Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK. (wikipedia.org)
  • In coordination chemistry, a ligand is an ion or molecule (see also: functional group) that binds to a central metal atom to form a coordination complex. (phys.org)
  • Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). (biomedcentral.com)
  • Differences in Volumetric Percent Density by Tertiles of Circulating RANK and sRANKL. (aacrjournals.org)
  • Least Square Means of Non-Dense Volume by Tertiles of Circulating RANK and sRANKL. (aacrjournals.org)
  • We, therefore, investigated the associations of circulating RANK and soluble RANK ligand (sRANKL) with mammographic density in premenopausal women. (aacrjournals.org)
  • We used linear regression models adjusted for confounders, to compare the least-square means of volumetric percent density across tertiles of circulating RANK and sRANKL. (aacrjournals.org)
  • Circulating RANK was positively associated with volumetric percent density, while circulating sRANKL was positively associated with volumetric percent density among women with higher progesterone levels. (aacrjournals.org)
  • Inhibition of RANK Ligand is a novel way of improving the rheumatoid arthritis patient. (healthcentral.com)
  • The TRANCE-RANK interaction regulates the expression of the anti-apoptotic molecule Bcl-xL. (thermofisher.com)
  • RANK-Ligand stands for receptor activator of NF-κB ligand, also termed TNSFSF11 or TRANCE. (miltenyibiotec.com)
  • The TRANCE-RANK interaction regulates the expression of the anti-apoptotic molecule Bcl-xL.Applications Reported: The MIH24 antibody has been reported for use in flow cytometric analysis, and ELISA.Applications Tested: The MIH24 antibody has been tested by flow cytometric analysis of human RANKL transfected cells. (fishersci.co.uk)
  • Antibodies that detect RANKL (RANK Ligand) can be used in several scientific applications, including Western Blot, ELISA, Flow Cytometry, Immunohistochemistry (Paraffin) and Immunocytochemistry. (thermofisher.com)
  • These antibodies target RANKL (RANK Ligand) in Human, Mouse and Rat samples. (thermofisher.com)
  • Our RANKL (RANK Ligand) monoclonal, polyclonal and recombinant monoclonal antibodies are developed in Mouse, Rabbit, Rat and Goat. (thermofisher.com)
  • These antibodies have been verified by Neutralization to confirm specificity to RANKL (RANK Ligand). (thermofisher.com)
  • Choose from 1 of 40 RANKL (RANK Ligand) antibodies, which have been validated in experiments with 38 publications and 55 images featured in our data gallery. (thermofisher.com)
  • This year so far, Ligand has entered into a worldwide OmniAb platform license agreement with Glenmark Pharmaceuticals per which the latter will be able to use the its full OmniAb platform to discover fully human mono- and multispecific antibodies. (yahoo.com)
  • Ligands in a complex dictate the reactivity of the central atom, including ligand substitution rates, the reactivity of the ligands themselves, and redox. (phys.org)
  • In addition, RANK Ligand is expressed by some T cells is a dendritic cell survival factor and is involved in the regulation of T cell-dependent immune response. (cellsciences.com)
  • RANK-Ligand is expressed by T helper cells and is involved in dendritic cell maturation. (miltenyibiotec.com)
  • T cell expression of RANK Ligand promotes dendritic cell maturation. (shenandoah-bt.com)
  • The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. (phys.org)
  • This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. (ligand.com)
  • Ligand expects Vernalis' technology to boost the company's long-term milestones and royalties potential. (nasdaq.com)
  • In March 2019, Ligand sold all rights to blockbuster drug, Promacta, to privately-held Royalty Pharma for $827 million. (nasdaq.com)
  • Targeting RANK Ligand directly affects the mechanism responsible for the loss of cartilage and bone in long-term rheumatoid arthritis. (healthcentral.com)
  • Some studies demonstrated that U-266 myeloma cell line and primary myeloma cells expressed RANK and RANKL. (sid.ir)
  • Results: Hematopoietic stem cells expressed RANK before and after differentiation into osteoclast. (sid.ir)
  • RANK-Ligand is expressed in several tissues and cell types, including fibroblasts, T cells, and osteoblasts, and functions by binding its cell surface signaling receptor RANK. (miltenyibiotec.com)
  • Human RANK-Ligand shares with mouse 85% amino acid identity and is reactive on murine cells. (miltenyibiotec.com)
  • This review will summarize our current knowledge of the role of the OPG/RANK-RANKL pathway in B cells in health and disease, and the contribution of B cells to HIV-induced bone loss. (frontiersin.org)
  • Using the enzyme fragment complementation technology, simply infect your target cells with the PathHunter β-Arrestin Retroparticles, transfect the cells with a GPCR plasmid, and perform a PathHunter GPCR β-arrestin assay with your ligand of interest. (discoverx.com)
  • Cells expressing CHRM2-PK fusion proteins were infected with PathHunter β-Arrestin2 Retroparticles and tested using 3 ligands: acetylcholine, carbachol and oxotremorine-M (oxo-M). Both pathway assays showed agonist pharmacology for all 3 ligands. (discoverx.com)
  • The stromal cells also divide to produce pre-osteoblasts, which express RANK-ligand (RANK-L) on their cell surfaces. (washington.edu)
  • The lining cells that were activated during Origination secrete RANK-ligand, which may remain bound to the cell surface. (dentalcare.com)
  • In addition to directly signaling through RANK for macrophage differentiation, RANKL activates the adjacent lymphatic endothelial cells to create a niche environment for these specialized immune cells. (wikipedia.org)
  • We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences. (strath.ac.uk)
  • A novel docking challenge has been set by the Drug Design Data Resource (D3R) in order to predict the pose and affinity ranking of a set of Farnesoid X receptor (FXR) agonists, prior to the public release of their bound X-ray structures and potencies. (chemaxon.com)
  • In the second phase, 102 FXR agonists were ranked by decreasing affinity according to the Gibbs free energy of the corresponding GRIMselected poses, computed by the HYDE scoring function. (chemaxon.com)
  • VeraChem's state of the art computational chemistry software is capable of protein-ligand and host-guest binding affinity prediction, fast calculation of accurate partial atomic charges for drug-like compounds, computation of energies and forces with empirical force fields, automatic generation of alternate resonance forms of drug-like compounds, conformational search with the powerful Tork distort-minimize algorithm, and automatic detection of topological and 3D molecular symmetries. (verachem.com)
  • The pocket here is predefined as a 10 Å sphere, and the center of the pocket is either defined as the center of the supplied ligand molecule or explicitly given by the user. (silcsbio.com)
  • The patent describes LGD-4665 and other small-molecule TPO mimetic compounds discovered at Ligand, formulations involving these compounds, as well as methods of making and using the compounds and formulations. (ligand.com)
  • Receipt of this patent reflects our continued focus on innovation while strengthening our intellectual property portfolio, and covers a platform molecule that we believe has significant market potential," said John L. Higgins, President and Chief Executive Officer of Ligand Pharmaceuticals. (ligand.com)
  • Osteoblasts also secreted the RANK ligand binding protein, osteoprotegerin (data not shown), which decreases osteoclast formation. (aacrjournals.org)
  • Crystal structure of the extracellular domain of mouse RANK ligand at 2.2-A resolution. (ebi.ac.uk)
  • nhances the expression of stromal RANK ligand, both of which increase osteolytic bone degradation [34]. (psu.edu)
  • We present a simple, modular graph-based convolutional neural network that takes structural information from protein-ligand complexes as input to generate models for activity and binding mode prediction. (arxiv.org)
  • [11] The thermal stability of phosphines ligands is enhanced when they are incorporated into pincer complexes . (wikipedia.org)
  • The popularity and usefulness of phosphine complexes has led to the popularization of complexes of many related organophosphorus ligands. (wikipedia.org)
  • Most work focuses on complexes of triorganophosphines, but primary and secondary phosphines, respectively RPH 2 and R 2 PH, also function as ligands. (wikipedia.org)
  • RANKL is a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK, an apoptosis regulator gene and controls cell proliferation by modifying protein levels of ld4, ld2 and cyclin D1. (prospecbio.com)
  • RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls cell proliferation by modifying protein levels of Id4, Id2 and cyclin D1. (wikipedia.org)
  • Ligand had acquired OMT, Inc. in 2016, which added an antibody-generating platform, OmniAb, to its technology portfolio. (nasdaq.com)
  • Ligand also entered into a worldwide OmniAb platform license agreement with Ferring Pharmaceuticals and venBio Partners this year. (yahoo.com)