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 TNFRSF11Bgene. Osteoprotegerin is a cytokine receptor, and a member of the tumor necrosis factor (TNF) receptor superfamily.
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. Osteoprotegerin levels are influenced by voltage-dependent calcium channels Cav1.2. 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-RANKligand interaction between osteoblast/stromal cells and osteoclast precursors. This has the effect of inhibiting the differentiation of the osteoclast precursor into a mature osteoclast.
Osteoprotegerin production is stimulated in vivo by the female sex hormone estrogen, 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. Osteoprotegerin has been used experimentally to decrease bone resorption in women with postmenopausal osteoporosis and in patients with lytic bone metastases.
^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. PMID20447527.
Buckley KA, Fraser WD (2003). "Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers". Ann. Clin. Biochem.39 (Pt 6): 551–6. doi:10.1258/000456302760413324. PMID12564836.
Whyte MP, Mumm S (2005). "Heritable disorders of the RANKL/OPG/RANK signaling pathway". Journal of musculoskeletal & neuronal interactions4 (3): 254–67. PMID15615493.
Anandarajah AP, Schwarz EM (2006). "Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications". J. Cell. Biochem.97 (2): 226–32. doi:10.1002/jcb.20674. PMID16240334.
Baud'huin M, Duplomb L, Ruiz Velasco C, et al. (2007). "Key roles of the OPG-RANK-RANKL system in bone oncology". Expert Rev Anticancer Ther7 (2): 221–32. doi:10.1586/14737220.127.116.11. PMID17288531.
Tsuda E, Goto M, Mochizuki S, et al. (1997). "Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis". Biochem. Biophys. Res. Commun.234 (1): 137–42. doi:10.1006/bbrc.1997.6603. PMID9168977.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Tan KB, Harrop J, Reddy M, et al. (1998). "Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells". Gene204 (1–2): 35–46. doi:10.1016/S0378-1119(97)00509-X. PMID9434163.
Yamaguchi K, Kinosaki M, Goto M, et al. (1998). "Characterization of structural domains of human osteoclastogenesis inhibitory factor". J. Biol. Chem.273 (9): 5117–23. doi:10.1074/jbc.273.9.5117. PMID9478964.
Yasuda H, Shima N, Nakagawa N, et al. (1998). "Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro". Endocrinology139 (3): 1329–37. doi:10.1210/en.139.3.1329. PMID9492069.
Tomoyasu A, Goto M, Fujise N, et al. (1998). "Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor". Biochem. Biophys. Res. Commun.245 (2): 382–7. doi:10.1006/bbrc.1998.8443. PMID9571159.
Morinaga T, Nakagawa N, Yasuda H, et al. (1998). "Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor". Eur. J. Biochem.254 (3): 685–91. doi:10.1046/j.1432-1327.1998.2540685.x. PMID9688283.
Blázquez-Medela AM, López-Novoa JM, Martínez-Salgado C (July 2011). "Osteoprotegerin and diabetes-associated pathologies". Curr. Mol. Med.11 (5): 401–16. PMID21568931.