What does RANKL do to osteoblasts?
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.
Does RANKL activate osteoclasts?
The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases.
What is up regulated when RANK RANKL binding occurs?
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 RANKL inhibit osteoclasts?
RANKL also inhibits osteoclast apoptosis. RANK, the signaling receptor of RANKL, is expressed on the surface of osteoclast precursor cells, mature osteoclasts, dendritic cells and other tumor cells.
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 increases RANKL expression on osteoblasts?
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 stimulates RANK Ligand?
Abstract. 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 does RANKL bind?
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.
What increases RANKL expression in osteoblasts?
How are osteoclasts activated?
The mature, multinucleated osteoclast is activated by signals, which leads to initiation of bone remodelling (Fig. 2).
What stimulates RANKL?
RANKL expression is stimulated in osteoblast/stromal cells by most of the factors that are known to stimulate osteoclast formation and activity. It is highly expressed in lymph nodes, thymus and lung, and at low levels in a variety of other tissues including spleen and bone marrow [17].
How does rank and rankl work?
RANKL/RANK, Wnt/b-catenin, and Jagged1/Notch1 are 3 important pathways modulated by osteoblasts which affect the bone mass density via the regulation of osteoblasts and osteoclasts functions [8]. In the RANKL/RANK/OPG pathway, RANKL binds to RANK as its receptor and eventually leads to osteoclast precursor maturation.
What is the function of RANKL?
Function. 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.
Where is rankl found?
RANKL is expressed in several tissues and organs including: skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas.
What are osteoclasts activated by?
What stimulates osteoclast activity?
Osteoclastic activity is stimulated by cytokines such as IL-6 and RANK and inhibited by calcitonin.
How do osteoclasts resorb bone?
Osteoclasts resorb bone through the production of proteolytic enzymes and secretion of hydrogen ions into the localized microenvironment under the ruffled border. This extracellular lysosome that is formed beneath the ruffled border results in degradation of collagen and calcified matrix.
What are the functions of osteoclasts?
Osteoclasts are the cells that degrade bone to initiate normal bone remodeling and mediate bone loss in pathologic conditions by increasing their resorptive activity. They are derived from precursors in the myeloid/monocyte lineage that circulate in the blood after their formation in the bone marrow.
What is the function of RANKL in osteoblasts?
RANKL, the essential cue for osteoclast differentiation, is the membrane-bound factor expressed by osteoclastogenesis-supporting cells such as osteoblasts and osteocytes. In vivo evidence indicates that RANKL functions as the indispensable and irreplaceable in the program of osteoclast differentiation.
What is the function of ODF in osteoclast differentiation?
Osteoclast Differentiation Factor Osteoclast differentiation factor (ODF) is a key mediator of PTH-induced bone resorption. Inhibiting its action blocks the resorptive effects of PTH (33). ODF, together with colony-stimulating factor-1, is both necessary and sufficient to induce osteoclastogenesis.
Are M-CSF and RANKL essential osteoclastogenic molecules?
Macrophage colony-stimulating factor (M-CSF) and RANKL are essential osteoclastogenic molecules the lack of which develop an osteopetrotic phenotype.
Does NFATc1 play a role in osteoclastogenesis in vivo?
The essential role of the NFATc1 in osteoclastogenesis in vivo was subsequently proven by studies using adoptive transfer of fetal liver cell [ 32] and conditional NFATc1 knockout mice [ 33 ].