What increases RANKL expression?

What increases RANKL expression?

Since osteoblasts control the regulation of RANKL, the stimulation via cytokines and growth factors will then stimulate osteoblasts to increase the expression of RANKL, often while simultaneously reducing bone formation.

What increases RANKL expression in osteoblasts?

Receptor Activator of Nuclear κ B ligand (RANKL) In breast tumor induced osteolysis, studies have shown that tumor derived PTHrP can stimulate RANKL expression in osteoblasts and that the presence of RANKL on the osteoblast cell surface drives osteoclast maturation (Mundy, 2002).

What is RANK in bone formation?

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.

Who produces RANKL?

At around the same time when we had the first evidence that RANKL might play a part in osteoclast development, RANKL (TRANCE) was independently cloned by two other groups as a molecule expressed on the surface of activated T cells. Both soluble and membrane-bound RANKL is produced by activated CD4+ and CD8+ T cells.

What is RANKL in bone remodeling?

RANKL/RANK signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover. OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK.

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.

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.

Does osteoblast produce RANKL?

RANKL is expressed on osteoblasts and T cells. It binds the receptor RANK, which is produced on osteoclasts and their progenitors. RANKL is a member of the tumor necrosis factor (TNF) super-family and is produced on osteoblasts and T cells.

What is the role of RANKL in bone resorption?

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 difference between osteoprotegerin and RANKL?

RANKL binds RANK and stimulates osteoclastic bone resorption. Osteoprotegerin (OPG) inhibits osteoclast differentiation, fusion, and activation. decoy receptor produced by osteoblasts and stromal cells that binds to and sequesters RANKL.

Where is RANKL expressed in the body?

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.

How important is RANKL in tissue growth and immunity?

Variation in concentration levels of RANKL throughout several organs reconfirms the importance of RANKL in tissue growth (particularly bone growth) and immune functions within the body. The level of RANKL expression does not linearly correlate to the effect of this ligand.