Osteoprotegerin

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Osteoprotegerin, also known as osteoclastogenesis inhibitory factor (OCIF), is a cytokine and a member of the tumor necrosis factor (TNF) receptor superfamily. It 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.^[1] Osteoprotegerin inhibits the differentiation of macrophages into osteoclasts and also regulates the resorption of osteoclasts in vitro and in vivo. Osteoprotegerin is a RANK homolog, and works by binding to RANK ligand on osteoblast/stromal cells, thus blocking the RANK-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. Recombinant human osteoprotegerin specifically acts on bone, increasing bone mineral density and bone volume. Osteoprotegerin has been used experimentally to decrease bone resorption in women with postmenopausal osteoporosis and in patients with lytic bone metastases.

Osteoprotegerin production is stimulated in vivo by the female sex hormone estrogen,^[2] as well as the experimental osteoporosis drug, strontium ranelate.

[edit] References

• Khosla S. (2001), "Minireview: The OPG/RANKL/RANK System." Endocrinology, 142:5050-5055, PMID 11713196
• Schoppet M., et al. (2002), "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function." Arteriosclerosis, Thrombosis, and Vascular Biology, 22: 549-553, PMID 11950689