What is the RANK RANKL OPG pathway?
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.
Does OPG inhibit RANKL?
OPG has been found to bind RANKL with approximately 500-fold higher affinity than RANK [10]. Hence, OPG prevents RANKL from binding to its receptor RANK, inhibiting osteoclastogenesis and protecting the bone from excessive osteoclast-mediated resorption [11, 12].
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.
What is the 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.
What secretes 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).
What is RANK in 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].
When RANKL binds to RANK what occurs?
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.
What stimulates 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.
What is RANK pathway?
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 stimulates 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).
Where is OPG produced?
marrow
OPG is a soluble decoy receptor for RANKL that is also a member of the TNF receptor superfamily [38]. It is produced by OBL in the marrow and blocks the interactions of RANKL with RANK, limiting osteoclastogenesis.
What is OPG osteoporosis?
OPG deficiency causes osteoporosis in mice, and, when administered to ovariectomized rats, OPG decreases osteoclast activity and restores normal bone mass. OPG is produced by osteoblasts and arterial cells, and inhibits osteoclast function by neutralizing receptor activator of NF-kappa B ligand (RANKL).
What is rank and RANKL?
RANKL has been identified to affect the immune system and control bone regeneration and remodeling. RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls cell proliferation by modifying protein levels of Id4, Id2 and cyclin D1 .
What is the RANK pathway?
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 does RANKL mean?
Rankle(adj) to produce a festering or inflamed effect; to cause a sore; — used literally and figuratively; as, a splinter rankles in the flesh; the words rankled in his bosom. Rankle(verb) to cause to fester; to make sore; to inflame.
What is a RANKL inhibitor?
RANKL inhibitors are used to treat osteoporosis, breast cancer, lung cancer, and prostate cancer. They work by preventing bone fractures and by destroying cancer cells.