同: OPG

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/10 11:43:48」(JST)

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Not to be confused with Osteopontin (OPN).

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF), or tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), is a protein that in humans is encoded by the TNFRSF11B gene.^[1] Osteoprotegerin is a cytokine receptor, and a member of the tumor necrosis factor (TNF) receptor superfamily.

Structure

Osteoprotegerin is a basic glycoprotein comprising 401 amino acid residues arranged into 7 structural domains. It is found as either a 60-kDa monomer or 120-kDa dimer linked by disulfide bonds.^[2]

Function

Osteoprotegerin is a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL). By binding RANKL, OPG inhibits nuclear kappa B (NF-κB) which is a central and rapid acting transcription factor for immune-related genes, and a key regulator of inflammation, innate immunity, and cell survival and differentiation.^[3] Osteoprotegerin levels are influenced by voltage-dependent calcium channels Cav1.2.^[4] OPG can reduce the production of osteoclasts by inhibiting the differentiation of osteoclast precursors (osteoclasts are related to monocytes/macrophages and are derived from granulocyte/macrophage-forming colony units (CFU-GM)) into osteoclasts and also regulates the resorption of osteoclasts in vitro and in vivo. OPG binding to RANKL on osteoblast/stromal cells, blocks the RANKL-RANK ligand interaction between osteoblast/stromal cells and osteoclast precursors. This has the effect of inhibiting the differentiation of the osteoclast precursor into a mature osteoclast.

Regulation and therapeutic applications

Osteoprotegerin production is stimulated in vivo by the female sex hormone estrogen,^[5] as well as the osteoporosis drug, strontium ranelate. Denosumab is a pharmacologic agent that in essence acts like osteoprotegerin as a decoy receptor for osteoblastic RANKL.

Recombinant human osteoprotegerin specifically acts on bone, increasing bone mineral density and bone volume. Space shuttle flight STS-108 in 2001 tested the effects of osteoprotegerin on mice in microgravity, finding that it did prevent increase in resorption and maintained mineralization.^[6]^[7] Osteoprotegerin has been used experimentally to decrease bone resorption in women with postmenopausal osteoporosis and in patients with lytic bone metastases.

Clinical significance

Elevated OPG levels has been reported in heart diseases,^[8] in placebo effect serum responses in IBS patients (PMID 20028464) and in severe mental disorders.^[9]

References

^ Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (April 1997). "Osteoprotegerin: a novel secreted protein involved in the regulation of bone density". Cell 89 (2): 309–19. doi:10.1016/S0092-8674(00)80209-3. PMID 9108485.
^ Schoppet M, Preissner KT, Hofbauer LC (April 2002). "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function". Arterioscler. Thromb. Vasc. Biol. 22 (4): 549–53. doi:10.1161/01.ATV.0000012303.37971.DA. PMID 11950689.
^ Krakauer T (2008). "Nuclear factor-kappaB: fine-tuning a central integrator of diverse biologic stimuli". Int. Rev. Immunol. 27 (5): 286–92. doi:10.1080/08830180802317957. PMID 18853340.
^ PMID14525906
^ Khosla S (December 2001). "Minireview: the OPG/RANKL/RANK system". Endocrinology 142 (12): 5050–5. doi:10.1210/en.142.12.5050. PMID 11713196.
^ "Commercial Biomedical Testing Module: Effects of Osteoprotegerin on Bone Maintenance in Microgravity (CBTM)". U.S. National Aeronautics and Space Administration (NASA). http://www.nasa.gov/mission_pages/station/science/experiments/CBTM.html.
^ Bateman TA, Countryman S (April 2002). "Osteoprotegerin and bone loss associated with spaceflight". Drug Discov. Today 7 (8): 456–7. doi:10.1016/S1359-6446(02)02260-2. PMID 11965392.
^ Venuraju SM, Yerramasu A, Corder R, Lahiri A (May 2010). "Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity". J. Am. Coll. Cardiol. 55 (19): 2049–61. doi:10.1016/j.jacc.2010.03.013. PMID 20447527.
^ Hope S, Melle I, Aukrust P, Agartz I, Lorentzen S, Steen NE, Djurovic S, Ueland T, Andreassen OA (September 2010). "Osteoprotegerin levels in patients with severe mental disorders". J Psychiatry Neurosci 35 (5): 304–10. doi:10.1503/jpn.090088. PMC 2928283. PMID 20569643. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2928283/.

External links

Osteoprotegerin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

The effects of high fat, low carbohydrate and low fat, high carbohydrate diets on tumor necrosis factor superfamily proteins and proinflammatory cytokines in C57BL/6 mice.

Sirjani M1, Taleban FA2, Hekmatdoost A3, Amiri Z4, Pellizzon M5, Hedayati M6, Bidad K7, Shokouhi Shoormasti R8, Pourpak Z9.
Iranian journal of allergy, asthma, and immunology.Iran J Allergy Asthma Immunol.2014 Aug;13(4):247-55.
There has been considerable inconsistency regarding the potential relationship between dyslipidemia and bone metabolism. The inflammatory stimulation through the receptor activator of the nuclear factor kappa-B ligand (RANKL)/ receptor activator of the nuclear factor kappa-B (RANK)/ osteoprotegerin
PMID 24659160

Prevention and treatment of postmenopausal osteoporosis.

Tella SH1, Gallagher JC2.
The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2014 Jul;142C:155-170. doi: 10.1016/j.jsbmb.2013.09.008. Epub 2013 Oct 29.
In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initia
PMID 24176761

Raloxifene pharmacodynamics is influenced by genetic variants in the RANKL/RANK/OPG system and in the Wnt signaling pathway.

Mencej-Bedrač S, Zupan J, Mlakar SJ, Zavratnik A, Preželj J, Marc J.
Drug metabolism and drug interactions.Drug Metabol Drug Interact.2014 Jun 1;29(2):111-4. doi: 10.1515/dmdi-2013-0066.
Abstract Background: Raloxifene is a selective estrogen receptor (ER) modulator (SERM) used for the treatment of osteoporosis. However, its efficacy and also its safety vary greatly among treated patients, and it might be influenced by the individuals' genetic background. As the receptor activator o
PMID 24615483

Japanese Journal

デノスマブの作用機構とその臨床応用

安倍正博
血液内科 70(2), 279-284, 2015-02
NAID 40020385390

Osteoprotegerin: Osteo-Vascular Connection

Journal of Atherosclerosis and Thrombosis advpub(0), 2015
NAID 130004845537

Osteoprotegerin: Osteo-Vascular Connection

Journal of Atherosclerosis and Thrombosis 22(3), 233-234, 2015
NAID 130004721915

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★リンクテーブル★

リンク元	「破骨細胞分化抑制因子」「破骨細胞形成抑制因子」「オステオプロテジェリン」

「破骨細胞分化抑制因子」

Tumor necrosis factor receptor superfamily, member 11b
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	3URF
Identifiers
Symbols	TNFRSF11B; OCIF; OPG; TR1
External IDs	OMIM: 602643 MGI: 109587 HomoloGene: 1912 GeneCards: TNFRSF11B Gene
Gene Ontology
Molecular function	• receptor activity; • cytokine activity;
Cellular component	• extracellular region; • proteinaceous extracellular matrix; • extracellular space;
Biological process	• skeletal system development; • apoptotic process; • signal transduction; • response to nutrient; • extracellular matrix organization; • response to magnesium ion; • negative regulation of odontogenesis of dentin-containing tooth; • response to drug; • response to estrogen stimulus; • negative regulation of bone resorption; • response to arsenic-containing substance;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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