RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases

@article{Baudhuin2007RANKLRO,
  title={RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases},
  author={Marc Baud’huin and François Lamoureux and Laurence Duplomb and Françoise Redini and Dominique Heymann},
  journal={Cellular and Molecular Life Sciences},
  year={2007},
  volume={64},
  pages={2334-2350}
}
Abstract.1997 saw the identification of a novel set of proteins within the tumor necrosis factor (TNF)/TNF receptor families that are required for the control of bone remodeling. Therefore, these receptors, receptor activator of nuclear factor kappa B (RANK), osteoprotegerin (OPG) and their ligand RANK ligand (RANKL) became the critical molecular triad controlling osteoclastogenesis and pathophysiologic bone remodeling. However, the establishment of the corresponding knock-out and transgenic… 
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The function and regulation of osteoprotegerin, its role in pathological states--primarily in cardiovascular diseases--and its relevance as a marker of cardiovascular risk are summarized.
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Osteoprotegerin: multiple partners for multiple functions.
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TLDR
The aim of this article is to provide an overview of the main biochemical, physiological, and pathological aspects of OPG biology in cardiovascular disease.
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TLDR
The results link higher imunoexpression for RANKL compared to OPG in chronic periodontitis and in aggressive odontogenic tumors, and in less aggressive od ontogenic tumors a tendency for higher expression for OPG.
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TLDR
Interestingly, studies of genetically engineered mice demonstrated that RANKL-RANK signaling is also required for proper formation of a lactating mammary gland and, intriguingly, the development of mammary cancer.
Osteoprotegerin exposure at different stages of osteoclastogenesis differentially affects osteoclast formation and function
TLDR
The biological effects of OPG exposure at the various stages of osteoclast differentiation were varied, and included the enhanced adhesion and survival of preosteoclasts, the block of differentiation from the early to the terminal stages of fractures, and suppression of mature osteocline activation following OPG Exposure during the terminal differentiation stage, suggesting that the effects ofOPG exposure differ based on the stage of differentiation.
Skeletal and extraskeletal actions of denosumab
TLDR
The clinical approval of denosumab provides a novel option to treat bone diseases with a potent, targeted and reversible inhibitor of bone resorption, and the molecular and cellular basis of the RANKL/RANK/OPG system is summarized and preclinical and clinical studies on the skeletal actions of denOSumab are presented.
OPG/RANK/RANKL AXIS IN PERIODONTOLOGY
TLDR
The refore destruction of the periodontal tissues can be improved by blocking RANKL expression and function, and biologic approaches targeting RANKRANKL-OPG axis seem to be a new concept over the pathogenesis ofperiodontal lesions and future therapeutic options.
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References

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The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease
TLDR
OPG serum level is considered to be a stable and reliable indicator of the overall activity of the OPG/RANK/RankL axis and may find application as a biomarker of vascular risk and prognosis and RANKL in turn may be a suitable target for novel therapies.
Functional Dissection of Osteoprotegerin and Its Interaction with Receptor Activator of NF-κB Ligand*
TLDR
It is shown that OPG dimer formation is required for the mechanism of inhibition of the RANK-L/RANK receptor interaction, and that dimerization of OPG results from noncovalent interactions mediated by the death domains and to a lesser extent by a C-terminal heparin-binding region.
Circulating osteoprotegerin and soluble RANKL: do they have a future in clinical practice?
The discovery of the signalling system consisting of receptor activator of nuclear factor-KB ligand (RANKL), its receptor RANKL and its decoy receptor osteoprotegerin (OPG) has been a key step in the
Circulating osteoprotegerin and receptor activator for nuclear factor kappaB ligand: clinical utility in metabolic bone disease assessment.
TLDR
The clinical utility of serum OPG and sRANKL measurements as markers of disease activity requires additional investigation and rigorous testing of assays and identification of the sources of measurement variability are required.
Mechanisms of Disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis
TLDR
This review summarizes the current evidence of osteoprotegerin, RANK ligand and RANK involvement in the pathophysiology of skeletal metastasis, and of therapeutic targeting of this process.
Plasma levels of receptor activator of nuclear factor‐κB ligand and osteoprotegerin in patients with neuroblastoma
TLDR
It is confirmed that the production of OPG and RANKL is disregulated in neuroblastoma, and the OPG‐to‐RANKL ratio does not have a predictive value in detecting bone metastasis, but the measurement of the previously mentioned markers could be useful in decisions regarding the use of adjuvant therapies.
Receptor Activator of NF-κB Ligand and Osteoprotegerin Regulate Proinflammatory Cytokine Production in Mice1
TLDR
It is found that RANKL pretreatment suppressed production of proinflammatory cytokines in macrophages in response to stimulation by bacteria and their components and protected mice from LPS-induced death, revealing prophylactic potential of RankL in acute inflammatory diseases.
Cell-based assay strategy for identification of motif-specific RANK signaling pathway inhibitors.
TLDR
The current understanding of Rank signaling in osteoclasts is reviewed and the potential of RANK signaling pathways as therapeutic pathways is discussed and a strategy for constructing novel cell-based systems for identifying compounds inhibiting signaling from two recently identified RANK motifs through high throughput screening is described.
Osteoprotegerin Reduces the Serum Level of Receptor Activator of NF-κB Ligand Derived from Osteoblasts1
TLDR
The results suggest that OPG suppresses the shedding of RankL from osteoblasts and that the serum RANKL in OPG−/− mice exactly reflects the state of bone resorption.
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