How does RANK and RANKL work?
RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It is associated with bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development.
What is RANKL expression?
RANKL is a transmembrane protein expressed on the surface of osteoblasts [21] that can be shed from the plasma membrane by osteoclast-derived MMP-7 [22]. From: Bone Cancer, 2010.
What is RANKL in osteoporosis?
The interaction of RANK with its ligand (RANKL) has been identified as the final common pathway through which bone resorption is regulated [29]. By binding to its receptor RANK on osteoclastic precursors, RANKL controls the differentiation, proliferation, and survival of osteoclasts.
What is RANKL biology?
Receptor activator of NF-κB (RANK) ligand (RANKL) induces the differentiation of monocyte/macrophage-lineage cells into the bone-resorbing cells called osteoclasts.
What is the role of RANKL?
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.
What is the interaction between RANK and RANK important for?
RANK is expressed on the cell surface of mature and immature osteoclasts, while RANKL is expressed on bone stroma and osteoblasts. The interaction between RANK and RANKL leads to osteoclastogenesis and subsequent increased bone turnover.
Is RANKL a protein?
RANKL exists as a homotrimeric protein and is typically membrane-bound on osteoblastic and activated T cells or is secreted by some cells, such as activated T cells (43–45). The secreted protein is derived from the membrane form as a result of either proteolytic cleavage or alternative splicing (46).
What is the function of RANKL?
What causes the RANKL?
In inflammatory conditions, such as rheumatoid arthritis, the numbers of immune and accessory cells are increased in affected joints. Some of these cells produce RANKL in response to locally elevated levels of pro-inflammatory cytokines and other inflammatory mediators.
What produces RANKL?
What stimulates RANKL?
Receptor activator of NF-kappaB (RANK) ligand (RANKL), expressed by cells of the osteoblast lineage binds to RANK, induces signaling and a gene expression cascade that leads to osteoclast differentiation and activation.
What happens when RANKL RANK binding?
RANKL binds to RANK on the surface of osteoclast precursors and recruits the adapter protein, TRAP6, leading to activation of NF-κB through phosphorylation and inactivation of inhibitory kappa kinases (IKKs) and NF-κB inhibitory kinase (not shown here). This induces activation of c-Fos.
RANKL is a transmembrane molecule expressed by mesenchymal cell and lymphocytes. The soluble form of RANKL is a consequence of proteolytic cleavage. RANKL binds to RANK on hematopoietic cells and activates cytoplasmic adaptor proteins (e.g., tumor necrosis factor receptor-associated factor 6, TRAF6).
What is the RANKL/RANK pathway?
The RANKL/RANK/OPG pathway Understanding of osteoclast formation and activation has advanced considerably since the discovery of the RANKL/RANK/OPG system in the mid 1990s. Osteoblasts and stromal stem cells express receptor activator of NF-jB ligand (RANKL), which binds to its receptor, RANK, on the surface of osteoclasts an …
What is the role of RANKL in osteoimmunology?
The essentiality of RANKL in the bone and the immune systems lies at the root of the field of “osteoimmunology.” Furthermore, this cytokine functions beyond the domains of bone metabolism and the immune system, e.g., mammary gland and hair follicle formation, body temperature regulation, muscle metabolism, and tumor development.
What is the difference between OPG and RANKL?
RANKL, a member of the TNF family, triggers osteoclastogenesis by forming a complex with RANK, a member of the TNF receptor family. OPG is a decoy receptor of RANKL and inhibits osteoclast maturation.