Human recombinant OPG/Fc Chimera is a chimeric protein expressed in Sf 21 insect cells. It is composed of human osteoprotegerin fused to the carboxy-terminal 6X histidine-tagged Fc portion of human immunoglobulin G1 (IgG1) via a peptide linker . The mature recombinant OPG/Fc is a disulfide-linked homodimeric protein, with each monomer containing 623 amino acid residues, including 380 residues from mature OPG and 243 residues from the Fc protein and linker . The calculated molecular mass of mature OPG/Fc is approximately 71 kDa, but due to glycosylation, it migrates as a 77 kDa protein in SDS-PAGE under reducing conditions .
OPG functions primarily by inhibiting osteoclastogenesis, the process by which osteoclasts (bone-resorbing cells) are formed. It achieves this by binding to RANKL, thereby preventing RANKL from interacting with its receptor RANK on the surface of osteoclast precursors . This inhibition of the RANKL-RANK interaction prevents the differentiation and activation of osteoclasts, leading to decreased bone resorption and increased bone density .
Additionally, OPG has been shown to promote osteoclast apoptosis in vitro, further contributing to its role in maintaining bone homeostasis . The balance between OPG and RANKL is a key determinant in whether new bone tissue is formed or existing bone tissue is lost .
The therapeutic potential of OPG has been explored in various studies. For instance, daily injections of OPG in normal rats have been shown to significantly increase bone mineral density and bone volume while decreasing the number of osteoclasts . Furthermore, OPG injections have been found to prevent bone and cartilage destruction in mouse models of arthritis without preventing inflammation .
OPG also plays a role in preventing arterial calcification, highlighting its potential in treating cardiovascular diseases . The regulation of OPG expression is influenced by various factors, including glucocorticoids and estrogen. Glucocorticoids, which can cause bone loss, inhibit OPG gene expression and stimulate RANKL production, whereas estrogen, which helps prevent osteoporosis in menopausal women, stimulates OPG gene expression .
Osteoprotegerin (OPG)/Fc Chimera is supplied as a lyophilized powder and should be reconstituted using sterile phosphate-buffered saline (PBS) containing at least 0.1% human serum albumin or bovine serum albumin . The reconstituted solution should be stored at 2°C to 8°C for up to one month, and for extended storage, it should be frozen in working aliquots at -20°C . Repeated freezing and thawing are not recommended .