Osteoprotegerin (OPG), also known as tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), is a crucial protein involved in bone remodeling and homeostasis. It acts as a decoy receptor for receptor activator of nuclear factor kappa B ligand (RANKL), thereby inhibiting osteoclastogenesis and promoting osteoclast apoptosis .
OPG was independently discovered by two research teams in 1997. Boyle’s group identified it while generating transgenic mice overexpressing various TNF receptor cDNAs, and Tsuda’s group identified it as a repressor of osteoclast differentiation . The protein was named osteoprotegerin from the Latin words “osteo” (bone) and “protegere” (to protect) .
OPG plays a central role in bone remodeling, a biological mechanism where around 10% of total bone mass is renewed per year . This process involves a balance between osteoclasts, which resorb bone, and osteoblasts, which form new bone. OPG inhibits the activation of osteoclasts by neutralizing RANKL, thus preventing excessive bone resorption .
Human recombinant OPG, particularly the Hi-5 variant, is produced using advanced biotechnological methods. This recombinant form retains the biological activity of natural OPG and is used in various research and therapeutic applications . It is often tagged with a His-tag to facilitate purification and detection .
OPG has been extensively studied for its role in bone diseases such as osteoporosis and bone metastasis in cancer . It is also being explored as a potential therapeutic target for various cancers due to its involvement in tumor survival, epithelial to mesenchymal transition (EMT), neo-angiogenesis, invasion, and metastasis .