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RANKL has been identified to affect the immune system and control bone regeneration and remodeling. RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls cell proliferation by modifying protein levels of Id4, Id2 and cyclin D1.
OPG plays an important role in bone metabolism as a decoy receptor for RANKL in the RANK/RANKL/OPG axis, inhibiting osteoclastogenesis and bone resorption. [5] OPG has also been shown to bind and inhibit TNF-related apoptosis-inducing ligand (TRAIL) which is responsible for inducing apoptosis in tumour, infected and mutated cells. [10]
Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. RANK is the receptor for RANK-Ligand and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It is associated with bone ...
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.
Osteoprotegerin (OPG) binds RANKL before it has an opportunity to bind to RANK, and hence suppresses its ability to increase bone resorption. RANKL, RANK, and OPG are closely related to tumor necrosis factor and its receptors. The role of the Wnt signaling pathway is recognized, but less well understood.
Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a monocyte lineage, to fuse.
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 ...
Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts , thus requiring direct contact between these cells and osteoclast precursors .