Osteoprotegerin

Osteoprotegerin
Tumor necrosis factor receptor superfamily, member 11b
Identifiers
Symbols TNFRSF11B; MGC29565; OCIF; OPG; TR1
External IDs OMIM602643 MGI109587 HomoloGene1912 GeneCards: TNFRSF11B Gene
RNA expression pattern
PBB GE TNFRSF11B 204932 at tn.png
PBB GE TNFRSF11B 204933 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4982 18383
Ensembl ENSG00000164761 ENSMUSG00000063727
UniProt O00300 Q3UK97
RefSeq (mRNA) NM_002546.3 NM_008764.3
RefSeq (protein) NP_002537.3 NP_032790.3
Location (UCSC) Chr 8:
119.94 – 119.96 Mb
Chr 15:
54.08 – 54.11 Mb
PubMed search [1] [2]

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.

Contents

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 both act as decoy receptors 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] and in severe mental disorders.[9]

References

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ PMID14525906
  5. ^ Khosla S (December 2001). "Minireview: the OPG/RANKL/RANK system". Endocrinology 142 (12): 5050–5. doi:10.1210/en.142.12.5050. PMID 11713196. 
  6. ^ "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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2928283. 

Further reading

External links


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