OPG is a member of TNF receptor superfamily and is shown to be capable of inhibiting osteoclastogenesis. OPG lacks the transmembrane domain and is expressed as soluble dimers linked by a disulfide linked form by the penultimate cysteine residues at the C-termini.
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|Synonym:||TNFRSF11B, OCIF, TR1|
|MW (calculated):||46,600 daltons|
|MW. (SDS-PAGE):||50 Kd|
|Abs 0.1% (= 1 mg/ml):||1.22|
OPG is a member of TNF receptor superfamily and is shown to be capable of inhibiting osteoclastogenesis. OPG lacks the transmembrane domain and is expressed as soluble dimers linked by a disulfide linked form by the penultimate cysteine residues at the C-termini. Recombinant human OPG specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number.
OPG expresses abundantly in adult lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestine, thyroid, lymph node, trachea, adrenal gland, testis, and bone marrow, at much lower levels in brain, placenta and skeletal muscle. In cell culture, OPG is up-regulated by increasing calcium-concentration and estrogens in the medium and down-regulated by glucocorticoids.
The dimeric OPG acts as a decoy receptor for RANKL and thereby neutralizes RANKL’s function in osteoclastogenesis, inhibits the activation of osteoclasts, and leads to osteoclast apoptosis in vitro. It also acts as decoy receptor for TRAIL and protect against apoptosis. Defects in OPG are the cause of juvenile Paget disease (JPD) also known as hereditary hyperphosphatasia or chronic congenital idiopathic hyperphosphatasia.
Amino Acid Sequence.
1. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Simonet W.S., Lacey D.L., Dunstan C.R., Kelley M., Chang M.-S., Luethy R., Nguyen H.Q., Wooden S., Bennett L., Boone T., Shimamoto G., Derose M., Elliott R., Colombero A., Tan H.-L., Trail G., Sullivan J., Davy E. expand/collapse author list Boyle W.J. Cell 89:309-319 (1997)
2. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Yasuda H., Shima N., Nakagawa N., Mochizuki S., Yano K., Fujise N., Sato Y., Goto M., Yamaguchi K., Kuriyama M., Kanno T., Murakami A., Tsuda E., Morinaga T., Higashio K. Endocrinology 139:1329-1337 (1998)
3. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. Emery J.G., McDonnell P., Burke M.B., Deen K.C., Lyn S., Silverman C., Dul E., Appelbaum E.R., Eichman C., DiPrinzio R., Dodds R.A., James I.E., Rosenberg M., Lee J.C., Young P.R. J. Biol. Chem. 273:14363-14367 (1998)
4. Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin. Luan X., Lu Q., Jiang Y., Zhang S., Wang Q., Yuan H., Zhao W., Wang J., Wang X. J. Immunol. 189:245-252 (2012)