What does rank ligand stand for?
Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 …
What is the interaction between RANKL and RANK important for?
In addition to regulating DC functions, the RANKL and RANK interaction is critical for the development and organization of several lymphoid organs. The RANKL signal initiates the formation of clusters of lymphoid tissue inducer cells, which is crucial for lymph node organogenesis.
What is OPG in bone?
Osteoprotegerin (OPG) is secreted by osteoblasts and osteogenic stromal stem cells and protects the skeleton from excessive bone resorption by binding to RANKL and preventing it from interacting with RANK. The RANKL/OPG ratio in bone marrow is thus an important determinant of bone mass in normal and disease states.
What is the difference between RANK and RANKL?
RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. RANKL (receptor activator for nuclear factor κ B ligand) is found on the surface of stromal cells, osteoblasts, and T cells.
How do RANK ligand inhibitors work?
It is a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor, which binds to and inhibits osteoblast-produced RANKL, in turn reduces the binding between RANKL and osteoclast receptor RANK, therefore decreases osteoclast-mediated bone resorption and turnover.
What stimulates OPG?
In human and rodent osteoblast cells, estrogen stimulates OPG expression in an ER-dependent manner (13,14). Conversely, estrogen suppresses OPG production in MCF-7 breast cancer cell and in peripheral blood mononuclear cells (29,30), and ERα mediated the suppression of OPG in MCF-7 cells (29).
What is OPG hormone?
Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by the TNFRSF11B gene.
How are RANKL, RANK, and OPG related?
RANKL, RANK, and OPG belong to the TNF and its receptor superfamilies. As a TNF superfamily molecule, RANKL forms a homotrimer and binds to its receptors. RANK and OPG act as a monomer and homodimer, respectively. The crystal structures of the RANK–RANKL and OPG–RANKL complex have been resolved at 2.7 Å resolution [ 12 ].
How are RANKL and rank receptors cloned in humans?
At almost the same time, another group cloned the receptor gene using a human dendritic cell (DC) cDNA library and its ligand, using a cDNA library of a murine thymoma cell line. In this study, the pair of the ligand and its receptor was designated as RANKL and RANK.
Where does RANKL come from in bone tissue?
In bone tissue, RANKL is expressed by several types of cells including osteoblasts, osteocytes and immune cells. Among these cells, RANKL expression is higher in osteoblasts and osteocytes. In neonatal or young mice in their growth period, hypertrophic chondrocytes in the growth plate and osteoblasts are the major sources of RANKL.
Where is RANKL expressed in the immune system?
RANK is mainly expressed in osteoclast precursors, mature osteoclasts, and immune cells such as DCs, macrophages, and microglia. A recent study demonstrated that the osteoclast releases RANK-expressing extracellular vesicles, which interact with the RANKL on osteoblasts.