Osteoprotegerin

from Wikipedia, the free encyclopedia

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

structure

Osteoprotegerin is a basic glycoprotein with 401 amino acids, which are arranged in 7 domains. It is found as a 60 kDa monomer or 120 kDa dimer, linked with disulfide bridges.

function

Osteoprotegerin is a decoy receptor (decoy) for the receptor activator of nuclear factor kappa B ligand (RANKL) . By binding RANKL, OPG inhibits NF-κB , which is a central and rapidly acting transcription factor for genes of the immune system, as well as a key regulator for inflammatory reactions, immunity and cell survival and differentiation. The amount of osteoprotegerin is influenced by calcium channels such as Cav1.2 . OPG can regulate the production of osteoclasts by inhibiting the differentiation of osteoclast precursors. The OPG binding to RANKL on the osteoblast blocks the RANKL receptor interaction between osteoblasts and osteoclast precursors. This results in the inhibition of the differentiation of the osteoclast precursor to the osteoclast.

Regulation and therapeutic applications

The osteoprotegerin production is stimulated in vivo by the hormone estrogen and the drug strontium ranelate . Denosumab is a pharmaceutical that, like osteoprotegerin, acts as a decoy receptor for RANKL.

Recombinant human osteoprotegerin acts specifically on bones. It increases bone density and amount . The space shuttle flight STS-108 (2001) tested the effects of osteoprotegerin on mice in weightlessness. It was found that the mineralization in the bones was retained and the absorption of minerals was improved. Osteoprotegerin has also been used experimentally to help women with postmenopausal osteoporosis , or patients with bone metastases.

Clinical Significance

However, increased OPG levels have also been associated with heart disease and severe mental illness.

Individual evidence

  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: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density . In: Cell . 89, No. 2, April 1997, pp. 309-19. doi : 10.1016 / S0092-8674 (00) 80209-3 . PMID 9108485 .
  2. ↑ Schoppet M, Preissner KT, Hofbauer LC: RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function . In: Arterioscler. Thromb. Vasc. Biol . 22, No. 4, April 2002, pp. 549-53. doi : 10.1161 / 01.ATV.0000012303.37971.DA . PMID 11950689 .
  3. ↑ Krakauer T: Nuclear factor-kappaB: fine-tuning a central integrator of diverse biological stimuli . In: Int. Rev. Immunol. . 27, No. 5, 2008, pp. 286-92. doi : 10.1080 / 08830180802317957 . PMID 18853340 .
  4. ↑ Khosla S: Minireview: the OPG / RANKL / RANK system . In: Endocrinology . 142, No. 12, December 2001, pp. 5050-5. doi : 10.1210 / en.142.12.5050 . PMID 11713196 .
  5. ↑ Commercial Biomedical Testing Module: Effects of Osteoprotegerin on Bone Maintenance in Microgravity (CBTM) . US National Aeronautics and Space Administration (NASA). Archived from the original on August 23, 2007. Retrieved June 28, 2014.
  6. ↑ Bateman TA, Countryman S: Osteoprotegerin and bone loss associated with spaceflight . In: Drug Discov. Today . 7, No. 8, April 2002, pp. 456-7. doi : 10.1016 / S1359-6446 (02) 02260-2 . PMID 11965392 .
  7. ↑ Venuraju SM, Yerramasu A, Corder R, Lahiri A: Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity . In: J. Am. Coll. Cardiol. . 55, No. 19, May 2010, pp. 2049-61. doi : 10.1016 / j.jacc.2010.03.013 . PMID 20447527 .
  8. ↑ Hope S, Melle I, Aukrust P, Agartz I, Lorentzen S, Steen NE, Djurovic S, Ueland T, Andreassen OA: Osteoprotegerin levels in patients with severe mental disorders . In: J Psychiatry Neurosci . 35, No. 5, September 2010, pp. 304-10. doi : 10.1503 / jpn.090088 . PMID 20569643 . PMC 2928283 (free full text).