同: RANKL

WordNet

very offensive in smell or taste; "a rank cigar"
relative status; "his salary was determined by his rank and seniority"
a row or line of people (especially soldiers or police) standing abreast of one another; "the entrance was guarded by ranks of policemen"
take precedence or surpass others in rank (同)outrank
growing profusely; "rank jungle vegetation"
take or have a position relative to others; "This painting ranks among the best in the Western World"
very fertile; producing profuse growth; "rank earth"
a substance (an atom or molecule or radical or ion) that forms a complex around a central atom

PrepTutorEJDIC

〈C〉〈U〉『階級』,等級;)相対的な)『順位』,地位: / 〈U〉高い地位(身分) / 〈C〉〈U〉(人・物の)『列』,並び;(兵隊)の横列 / 《the ranks》(また『rank and file』)(将校たちに対して)兵卒,下士官 / …‘を'『並べる』 / …‘を'『位置づける』,評価する / 《米》…‘より'上位にある / 『位置する』・「pull one's rank on 誰々」で「(誰々に)地位を悪用する; (意見が衝突したような場合に)階級をかさに着て(誰々に)命令を押しつける」
(植物が)おい茂った,はびこった / (土地が)植物をおい茂らせた,肥えすぎた;(土地が)(植物を)おい茂らせた《+『with』+『名』》 / 悪臭を放つ,いやな味のする / 全くの,ひどい
Regular Army正規軍

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/25 22:13:52」(JST)

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[Wiki en表示]

Not to be confused with RANK, the osteoclast cell-surface receptor that binds to RANKL.

"TRANCE" redirects here. For other uses, see Trance (disambiguation).

Receptor activator of nuclear factor kappa-B 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.^[1]^[2]

Critical for adequate bone metabolism, this surface-bound molecule (also known as CD254) found on osteoblasts serves to activate osteoclasts, which are the cells involved in bone resorption. Osteoclastic activity is triggered via the osteoblasts' surface-bound RANKL activating the osteoclasts' surface-bound receptor activator of nuclear factor kappa-B (RANK).

Function[edit]

RANKL is 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. RANKL also has a function in the immune system, where it is expressed by T helper cells and is thought to be involved in dendritic cell maturation. This protein was shown to be a dendritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor 6 (TRAF6), which indicated this protein may have a role in the regulation of cell apoptosis.^[3]

Animal models[edit]

Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy.^[3]

Clinical significance[edit]

Bone[edit]

Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis and psoriatic arthritis. The first FDA-approved RANKL inhibitor was denosumab (to treat osteoporosis in post menopausal women).

Breast cancer[edit]

Treatment with medroxyprogesterone acetate (MPA), a synthetic progestin that is used in birth control pills and hormone replacement therapy, is associated with an increased risk of developing breast cancer. MPA causes a substantial induction of RANKL in mammary-gland epithelial cells while deletion of RANKL decreases the incidence MPA-induced breast cancer. Hence inhibition of RANKL has potential for the prevention and treatment of breast cancer.^[4]^[5]

References[edit]

^ Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS, Frankel WN, Lee SY, Choi Y (October 1997). "TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells". J. Biol. Chem. 272 (40): 25190–4. doi:10.1074/jbc.272.40.25190. PMID 9312132. Cite uses deprecated parameters (help)
^ Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L (November 1997). "A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function". Nature 390 (6656): 175–9. doi:10.1038/36593. PMID 9367155. Cite uses deprecated parameters (help)
^ ^a ^b "Entrez Gene: TNFSF11 tumor necrosis factor (ligand) superfamily, member 11".
^ Schramek D, Leibbrandt A, Sigl V, Kenner L, Pospisilik JA, Lee HJ, Hanada R, Joshi PA, Aliprantis A, Glimcher L, Pasparakis M, Khokha R, Ormandy CJ, Widschwendter M, Schett G, Penninger JM (November 2010). "Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer". Nature 468 (7320): 98–102. doi:10.1038/nature09387. PMID 20881962. Cite uses deprecated parameters (help)
^ Gonzalez-Suarez E, Jacob AP, Jones J, Miller R, Roudier-Meyer MP, Erwert R, Pinkas J, Branstetter D, Dougall WC (November 2010). "RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis". Nature 468 (7320): 103–7. doi:10.1038/nature09495. PMID 20881963. Cite uses deprecated parameters (help)

External links[edit]

RANKL Signaling Pathway
RANKL Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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1. 骨格の正常な発達および骨形成ならびに骨吸収の調節 normal skeletal development and regulation of bone formation and resorption
2. 骨粗鬆症に対するデノスマブ denosumab for osteoporosis
3. IL-1、IL-6、およびRANKLを抑制する生物学的製剤の関節リウマチにおけるランダム化臨床試験 randomized clinical trials in rheumatoid arthritis of biologic agents that inhibit il 1 il 6 and rankl
4. 骨転移の機序 mechanisms of bone metastases
5. 転移性癌患者におけるビスホスホネートおよびデノスマブ bisphosphonates and denosumab in patients with metastatic cancer

English Journal

Regulation of Osteoblast Migration Involving Receptor Activator of Nuclear Factor-kappa B (RANK) Signaling.

Golden D1, Saria EA1, Hansen MF1.
Journal of cellular physiology.J Cell Physiol.2015 Dec;230(12):2951-60. doi: 10.1002/jcp.25024.
Bone remodeling requires osteoclast activation, resorption, and reversal, prior to osteoblast migration into the bone pit. The Receptor Activator of NF-κB (RANK) signaling pathway plays an important role in bone remodeling. Two components of the RANK signaling pathway, RANK Ligand (RANKL) and the d
PMID 25893522

Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis.

Yang CY1,2,3, Chang ZF4, Chau YP5, Chen A6, Lee OK7,8,9,10,11, Yang AH12,13,14.
Calcified tissue international.Calcif Tissue Int.2015 Nov;97(5):466-75. doi: 10.1007/s00223-015-0030-5. Epub 2015 Jul 1.
Uremic patients are predisposed to atrophy of the alveolar bone and narrowing of the dental pulp chamber. Such pulp chamber changes have only been diagnosed radiologically; however, this has not been supported by any pathological evidence. We used a uremic rat model with secondary hyperparathyroidis
PMID 26126938

Correlating RANK Ligand/RANK Binding Kinetics With Osteoclast Formation and Function.

Warren JT1, Zou W1, Decker CE2, Rohatgi N1, Nelson CA1, Fremont DH1, Teitelbaum SL1,3.
Journal of cellular biochemistry.J Cell Biochem.2015 Nov;116(11):2476-83. doi: 10.1002/jcb.25191.
The interaction between Receptor Activator of NF-κB Ligand (RANKL) and its receptor RANK is essential for the differentiation and bone resorbing capacity of the osteoclast. Osteoprotegerin (OPG), a soluble homodimer, acts as a decoy receptor for RANKL and thus inhibits osteoclastogenesis. An imbala
PMID 25864714

Japanese Journal

Plasma Hepatocyte Growth Factor Elevation May Be Associated with Early Metastatic Disease in Primary Lung Cancer Patients

Hosoda Hiroshi,Izumi Hiroyuki,Tukada Yoshikazu,Takagiwa Jun,Chiaki Tomoshige,Yano Makoto,Arai Hirokuni
Annals of Thoracic and Cardiovascular Surgery advpub(0), 1109270092, 2011
… Purpose: Hepatocyte growth factor (HGF), a ligand of the c-met proto-oncogene, exhibits activating effects on human lung cancer both in vitro and in vivo. … Survival curve analysis revealed that patients with a high level of HGF (over the cutoff value) exhibited a poor prognosis of metastatic disease, compared to those in the low-level group after curative surgery (log rank test, P = 0.020; …
NAID 130001085312

抗RANKリガンド抗体(denosumab)

中山耕之介
内分泌・糖尿病・代謝内科 31(5), 499-508, 2010-11
NAID 40018275461

「osteoclast differentiation factor」

Tumor necrosis factor (ligand) superfamily, member 11
	; PDB rendering based on 1s55.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	3URF
Identifiers
Symbols	TNFSF11; CD254; ODF; OPGL; OPTB2; RANKL; TRANCE; hRANKL2; sOdf
External IDs	OMIM: 602642 MGI: 1100089 HomoloGene: 2744 GeneCards: TNFSF11 Gene
Gene Ontology
Molecular function	• cytokine activity; • tumor necrosis factor receptor binding; • tumor necrosis factor receptor superfamily binding;
Cellular component	• extracellular region; • extracellular space; • cytoplasm; • integral to plasma membrane;
Biological process	• ossification; • monocyte chemotaxis; • immune response; • activation of JUN kinase activity; • organ morphogenesis; • positive regulation of intracellular protein kinase cascade; • cytokine-mediated signaling pathway; • osteoclast differentiation; • tumor necrosis factor-mediated signaling pathway; • mammary gland epithelial cell proliferation; • positive regulation of homotypic cell-cell adhesion; • positive regulation of I-kappaB kinase/NF-kappaB cascade; • positive regulation of MAP kinase activity; • bone resorption; • positive regulation of osteoclast differentiation; • positive regulation of bone resorption; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of JNK cascade; • positive regulation of T cell activation; • positive regulation of sequence-specific DNA binding transcription factor activity; • positive regulation of NF-kappaB transcription factor activity; • protein homooligomerization; • positive regulation of corticotropin-releasing hormone secretion; • positive regulation of protein kinase B signaling cascade; • mammary gland alveolus development; • ERK1 and ERK2 cascade; • positive regulation of fever generation by positive regulation of prostaglandin secretion; • TNFSF11-mediated signaling pathway; • positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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