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RANKL, through its ability to stimulate osteoclast formation and activity, is a critical mediator of bone resorption and overall bone density. Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis and psoriatic arthritis .
An overexpression of RANKL can cause an overproduction and activation of osteoclasts, which break down bone. The balance between RANKL and OPG is a target for therapy in many diseases including estrogen deficiency-associated osteoporosis, rheumatoid arthritis, Paget's disease, periodontal disease, and bone tumors and malignancies.
An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have four nuclei [5] and are 150–200 μm in diameter. When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 μm in diameter occur. These may have dozens of nuclei, and typically express major ...
As a decoy receptor for RANKL, OPG inhibits RANK-RANKL interactions thus suppressing osteoclastogenesis and bone resorption. [32] OPG is also a decoy receptor for TRAIL, another regulator of osteoclastogenesis in osteoclast precursor cells [35] and an autocrine signal for mature osteoclast cell death. [36]
Denosumab is an inhibitor of RANKL (receptor activator of nuclear factor kappa-Β ligand), [11] which works by decreasing the development of osteoclasts, which are cells that break down bone. Denosumab is a human monoclonal IgG2 antibody that targets the protein RANKL, which is essential for the formation, function and survival of osteoclasts ...
The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These are the cells responsible for the resorption of bone. Osteoblasts are generally present on the outer layer of bone, just beneath the periosteum. Attachment of the osteoclast to the osteon begins the process.
The activation of osteoclasts is regulated by various molecular signals, of which RANKL (receptor activator of nuclear factor kappa-B ligand) is one of the best-studied. [100] This molecule is produced by osteoblasts and other cells (e.g. lymphocytes), and stimulates RANK (receptor activator of nuclear factor κB).
The RANKL-RANK-OPG axis (OPG stands for osteoprotegerin) is an example of an important signaling system functioning both in bone [6] and immune cell communication. RANKL is expressed on osteoblasts and activated T cells, whereas RANK is expressed on osteoclasts, and dendritic cells (DCs), both of which can be derived from myeloid progenitor cells.