What is the signaling pathway for RANKL?

What is the signaling pathway for RANKL?

In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand (RANKL; also known as TNFSF11) binding to its receptor RANK (also known as TNFRSF11A) drives osteoclast development as the crucial signaling pathway.

What happens when RANK binds to RANKL?

RANKL binds to RANK and activates cytoplasmic adaptor proteins (e.g., tumor necrosis factor receptor-associated factor 6). Downstream signaling pathways include NF-κB, mitogen-activated protein kinase family, and nuclear factor of activated T cells, cytoplasmic 1. RANKL is neutralized by its soluble decoy receptor OPG.

What is RANKL RANK OPG pathway?

The RANK/RANKL/OPG Pathway The RANKL/RANK/OPG system is known for its roles in osteoclasts maturation, bone modeling, and bone remodeling. Receptor activator of NF-kB (RANK), receptor activator of NF-kB ligand (RANKL), and osteoprotegerin (OPG) are the main components of this signaling system.

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. RANKL (receptor activator for nuclear factor κ B ligand) is found on the surface of stromal cells, osteoblasts, and T cells.

What is a RANK Ligand inhibitor?

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 produces RANK Ligand?

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).

Does OPG bind to RANK or RANKL?

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 role of RANK RANKL and OPG in bone formation?

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.

Does OPG inhibit RANKL?

OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK.

Does estrogen increase OPG?

Estrogen stimulates OPG expression mainly at a transcriptional level through the estrogen receptor (ER), particularly ERα (13–15,18). Furthermore, an estrogen response element has been identified in the OPG promoter (19).

What is the interaction between RANK and RANK important for?

This signaling system is essential for skeletal homeostasis, and disruption of it leads to inhibition of bone resorption in vitro and in animal models of most bone diseases characterized by increased resorption. RANKL/RANK signaling plays important roles in tissues other than bone.

What is rank osteoporosis?

Receptor activator of nuclear factor-κB (RANK) is a member of the tumor necrosis factor family expressed by osteoclasts and their precursors [29]. The interaction of RANK with its ligand (RANKL) has been identified as the final common pathway through which bone resorption is regulated [29].

What are the roles of RANKL RANK and OPG?

RANKL/RANK signaling also regulates lymph node formation and mammary gland lactational hyperplasia in mice, and OPG protects large arteries of mice from medial calcification. This article reviews the roles of the RANKL/RANK/OPG system in bone and other tissues.

What does RANKL do to the osteoblasts?

Osteoblasts produce. 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 does RANKL bind to the NF-JB receptor?

Osteoblasts and stromal stem cells express receptor activator of NF-jB ligand (RANKL), which binds to its receptor, RANK, on the surface of osteoclasts and their precursors.

Why is the RANKL / OPG ratio important in bone marrow?

The RANKL/OPG ratio in bone marrow is thus an important determinant of bone mass in normal and disease states. RANKL/RANK signaling also regulates lymph node formation and mammary gland lactational hyperplasia in mice, and OPG protects large arteries of mice from medial calcification.