OPG-2

Osteoprotegerin (OPG), also called OCIF (osteoclastogenesis inhibitory factor) is a secreted 55-60 kDa protein that regulates bone density. As a member of the tumor necrosis factor receptor (TNFR) superfamily of proteins, it is designated TNFRSF11B. Human OPG cDNA encodes 401 amino acids (aa) including a 21 aa signal peptide and a 380 aa mature soluble protein with four TNFR domains, two death domains and a heparin-binding region. The cysteine-rich TNFR domains are essential for ligand interaction, while a cysteine at the C-terminus mediates homodimerization. Mature human OPG shares 86%, 87%, 92%, 92% and 88% amino acid sequence identity with mouse, rat, equine, canine and bovine OPG, respectively. OPG is widely expressed and constitutively released as a homodimer by mesenchymal stem cells, fibroblasts and endothelial cells. Regulation of its expression by estrogen, parathyroid hormone and cytokines is complex and changes with age. OPG has been called a decoy receptor for the TNF superfamily ligands, TRANCE (tumor necrosis factor-related activation-induced cytokine), also called RANK L (receptor activator of NF kappa B ligand), and TRAIL (TNF-related apoptosis-inducing ligand), which also bind TNF family receptors RANK and TRAIL receptors 1-4, respectively. TRAIL decreases the release of OPG from cells that express it, while OPG inhibits TRAIL-induced apoptosis. Expression of RANK L on the cell surface, and thus its ability to stimulate osteoclastogenesis, is regulated by OPG by intracellular and extracellular mechanisms. Within osteoblasts, interaction of the basic domain of OPG with RANK L in the Golgi inhibits RANK L secretion. Extracellularly, OPG binding to RANK L results in clathrin-mediated internalization and degradation of both proteins. Binding of OPG by syndecan-1 heparin sulfates on multiple myeloma cells also results in OPG internalization and degradation, contributing to bone loss.

Approximately 109.6 kDa.

Sterile Filtered White lyophilized (freeze-dried) powder.

> 95 % by SDS-PAGE and HPLC analyses.