Osteoprotegerin also known as OPG, is a protein that is encoded by the TNFRSF11B gene in humans. OPG is a cytokine receptor and is also a member of the tumor necrosis factor receptor superfamily, also known as the TNF family.
OPG is known as a basic glycoprotein which is comprised of 401 amino acid residues and is arranged into 7 different structural domains. It can be found as a 60-kDa monomer or 120-kDa dimer which is linked by disulfide bonds.
OPG is a decoy receptor, made for the receptor activator of nuclear factor kappa B ligand (also known as (RANKL). By binding RANKL, OPG is able to prevent RANK-mediated nuclear factor kappa B from activating, which is a fast-acting transcription factor which is designed for immune-related genes and is also a key regulator of innate immunity, cell survival and differentiation, and inflammation.
OPG levels are impacted by voltage-dependent calcium channels. OPG is able to reduce the creation of osteoclasts by stopping the differentiation of osteoclast precursors into osteoclasts. It also helps to regulate the resorption of osteoclasts in vivo and in vitro. OPG binding to RANKL via stomal and osteoblast cells blocks the RANKL-RANK interaction between these cells and osteoclast precursors.
How is osteoprotegerin production simulated? OPG production is stimulated in vivo by estrogen, the female sex hormone, in addition to the osteoporosis drug, strontium ranelate. Denosumab, a pharmacological agent that acts like osteoprotegerin as a decoy receptor for osteoblast RANKL.
Studies have shown that recombinant human osteoprotegerin acts specifically on bone, increasing the bone mineral density, in addition to bone volume. In 2001, a space shuttle flight tested its effects on mice in microgravity and found that it OPG did increase resorption and maintained mineralization. OPG has been used in an experimental way to reduce bone resorption in women suffering from postmenopausal osteoporosis, as well as in patients with lytic bone metastases.
Why is OPG clinically significant? It has been reported that when it comes to heart disease, and other cardiovascular problems, increased levels of OPG have been reported. As well as in placebo effect serum responses in patients with Irritable Bowel Syndrome, and also in serious mental disorders. It has also been noted that mutations in TNFRSF11B are linked to osteoarthritis in someway. Research has found that OPG is expressed on mesenchymal stem cells, which means that they mediate their supportive effect on osteoclastogenesis.
More recently, it has been suggested that OPG may be the link between bone and cardiovascular diseases, such as heart attacks and other heart problems. Studies have suggested that it is particularly closely linked to an increase in cardiovascular risk in patients who suffer from diabetes or insulin resistance.
Studies have shown that OPG, produced by osteoblasts is an important regulatory factor in osteoclast development and function. What recent scientific findings show is that OPG produced by stromal cells or osteoblasts is an important regulator of osteoclast differentiation and function. It also shows that RANKL expressed by these osteoblasts has the ability to function as a membrane-associated form.