Why do osteoblasts produce RANKL?

Why do osteoblasts produce RANKL?

RANKL is expressed on osteoblasts and T cells. It binds the receptor RANK, which is produced on osteoclasts and their progenitors. The interaction of RANK with RANKL is required for osteoclast formation, differentiation, activation and survival.

What increases RANKL expression in osteoblasts?

Regulation of osteoclast formation and activation. This is based on studies showing that, after PTH injection, RANKL expression is increased by osteoblast/stromal cells, leading to activation of existing osteoclasts and release by them of a factor(s) that stimulates new bone formation.

What does RANKL do to osteoclast?

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.

Do osteoblasts release RANKL?

RANKL is released by bone-forming cells known as osteoblasts and stimulates RANK on the surface of stem cells to form osteoclasts, which are cells that mediate bone resorption. The same pair of proteins can also signal in reverse.

What stimulates RANKL?

Parathyroid hormone (PTH) stimulates osteoclast formation by binding to its receptor on stromal/osteoblastic cells and stimulating the production of receptor activator of NFkappaB ligand (RANKL) and inhibiting the expression of osteoprotegerin (OPG).

What activates RANKL?

High protein expression of RANKL is commonly detected in the lungs, thymus and lymph nodes. Osteoclastic activity is triggered via the osteoblasts’ surface-bound RANKL activating the osteoclasts’ surface-bound receptor activator of nuclear factor kappa-B (RANK).

Does osteoprotegerin stimulate bone resorption?

OPG is a new member of the tumor necrosis factor (TNF) receptor family which plays a key role in the physiological regulation of osteoclastic bone resorption. Excess OPGL increases bone resorption, whereas excess OPG inhibits resorption.

What stimulates bone resorption?

Hormones play a role in determining when bones go through resorption or formation. These include parathyroid hormone (PTH) and calcitonin. When the level of calcium in the blood is low, the parathyroid activates to release PTH which stimulates osteoclasts to remove bone, thus releasing calcium into the bloodstream.

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.

Who produces RANKL?

synovial fibroblasts
In this context, RANKL that mediate osteoclastogenesis is produced by the synovial fibroblasts under inflammation, as well as T helper 17 (TH17) cells, especially those that with a history of Foxp3 expression (exFoxp3 TH17 cells) (Fig. 1c) [48,49,50].

Does estrogen inhibit bone resorption?

The main effect of estrogen is to inhibit bone remodeling, likely via the osteocyte. Estrogen also inhibits bone resorption, principally by directs effects on osteoclasts, although effects of estrogen on osteoblast/osteocyte and T-cell regulation of osteoclasts likely also play a role.

What cell makes osteoprotegerin?

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.

How does osteoblasts control the expression of RANKL?

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.

Where does RANKL bind in the myeloid lineage?

RANKL is a member of the tumor necrosis factor (TNF) cytokine family, it binds to RANK on cells of the myeloid lineage and functions as a key factor for osteoclast differentiation and activation. RANKL may also bind to osteoprotegerin, a protein secreted mainly by cells of the osteoblast lineage which is a potent inhibitor

Which is a major source of RANKL in bone remodeling?

Recent studies suggest that in postnatal bones, the osteocyte is the major source of RANKL regulating bone remodeling. RANKL derived from other cell types contributes to bone loss in conditions involving inflammation such as rheumatoid arthritis, and in lytic lesions caused by cancer, such as in multiple myeloma .

What is the function of RANKL in the immune system?

RANKL may also bind to osteoprotegerin, a protein secreted mainly by cells of the osteoblast lineage which is a potent inhibitor of osteoclast formation by preventing binding of RANKL to RANK. RANKL also has a function in the immune system, where it is expressed by T helper cells and is thought to be involved in dendritic cell maturation.