Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Hepatocellular Carcinoma With Bone Metastasis

2006 ◽  
Vol 14 (3) ◽  
pp. 1191-1199 ◽  
Author(s):  
Atsushi Sasaki ◽  
Kenji Ishikawa ◽  
Naotsugu Haraguchi ◽  
Hiroshi Inoue ◽  
Tetsuya Ishio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Metastasis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Receptor Activator

Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis

2011 ◽  
Vol 71 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Maria J H Boumans ◽  
Rogier M Thurlings ◽  
Lorraine Yeo ◽  
Dagmar Scheel-Toellner ◽  
Koen Vos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Osteoclast Precursors ◽  
Receptor Activator ◽  
Hands And Feet

ObjectivesTo examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients.MethodsTwenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp–van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor κB ligand (RANKL), osteocalcin and cross-linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment.ResultsAfter 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor κB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p<0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change.ConclusionsRituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA.

scholarly journals Role of Prostaglandin E in Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Osteoblasts Induced by Cell Adhesion to Bone Marrow B-lymphocytes

2009 ◽  
Vol 55 (5) ◽  
pp. 832-837 ◽  
Author(s):  
Michiko Hirata ◽  
Suguru Harada ◽  
Chiho Matsumoto ◽  
Morichika Takita ◽  
Chisato Miyaura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
B Lymphocytes ◽  
Nuclear Factor Κb ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Receptor Activator

scholarly journals Colony-Stimulating Factor-1 (CSF-1) Directly Inhibits Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression by Osteoblasts

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 4977-4988 ◽  
Author(s):  
Y. Wittrant ◽  
Y. Gorin ◽  
S. Mohan ◽  
B. Wagner ◽  
S. L. Abboud-Werner
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Wild Type ◽  
Rankl Expression ◽  
Nadph Oxidase Activity ◽  
Rankl Mrna ◽  
Receptor Activator ◽  
Bone Marrow Cultures ◽  
Stimulating Factor

Colony-stimulating factor-1 (CSF-1), released by osteoblasts, stimulates the proliferation of osteoclast progenitors via the c-fms receptor (CSF-1R) and, in combination with receptor activator of nuclear factor-κB ligand (RANKL), leads to the formation of mature osteoclasts. Whether the CSF-1R is expressed by osteoblasts and mediates specific biological effects in osteoblasts has not been explored. Wild-type primary calvaria osteoblasts (OB) were analyzed for CSF-1R expression (RT-PCR and Western blot) and functionality (immunocomplex kinase assay). OB were serum starved for 24 h, and the effect of CSF-1 (0–100 ng/ml) on OB biological activities was determined at 48 h. In wild-type mouse bone marrow cultures, CSF-1 was tested for its effect on RANKL mRNA and osteoclast formation. Because ROS influence osteoblast RANKL expression, studies analyzed the effect of CSF-1 on reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and Nox1 and Nox4 proteins. Results indicate that OB express CSF-1R mRNA and protein and that CSF-1R could be phosphorylated in the presence of CSF-1. In osteoblasts, CSF-1 decreased RANKL mRNA in a dose- and time-dependent manner. Incubation of bone marrow cultures with CSF-1 resulted in a significant decline in tartrate-resistant acid phosphatase (TRACP) activity and CTR expression. RANKL-decreased expression by CSF-1 was correlated with a decrease of NADPH oxidase activity as well as Nox1 and Nox4 protein levels. These findings provide the first evidence that osteoblasts express CSF-1R and are a target for CSF-1 ligand. CSF-1-mediated inhibition of RANKL expression on osteoblasts may provide an important mechanism for coupling bone formation/resorption and preventing excessive osteoclastogenesis during normal skeletal growth.

scholarly journals Increased thyroglobulin and receptor activator of nuclear factor kappa B ligand expression is a risk factor of bone metastasis on patients with thyroid cancer

2021 ◽  
Vol 9 (5) ◽  
pp. 1244
Author(s):  
Gede Ketut Alit Satria Nugraha ◽  
Putu Astawa ◽  
Made Bramantya Karna ◽  
I. Gede Eka Wiratnaya ◽  
I. Wayan Juli Sumadi
Keyword(s):  
Risk Factor ◽  
Thyroid Cancer ◽  
Bone Metastasis ◽  
Nuclear Factor Kappa B ◽  
High Expression ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Cutoff Value ◽  
Increased Risk ◽  
Receptor Activator

Background: Metastatic bone disease (MBD) of thyroid cancer poses increased risk of morbidity and mortality and significant decrease of quality of life of the patient, with 10 years survival rate of 40-70%. This study aims to find correlation between increased expression of thyroglobulin and receptor activator of nuclear factor kappa B ligand (RANKL) on thyroid cancer biopsy and increased risk of bony metastasis.Methods: This study use case control design to analyze the histopathologic preparation taken from biopsy of the patients with thyroid cancer from 2015 until 2020. The histopathology preparation was cut with 4 µm thickness, then analyzed through immunohistochemistry assay using thyroglobulin antibody cocktail and anti-RANKL polyclonal antibody by a pathologic anatomy consultant. Analysis and correlation between the high thyroglobulin and RANKL expression with the incidence of bony metastasis using chi-squared test and odd ratio calculation.Results: There is a significant difference of thyroglobulin and RANKL expression between the group with metastasis and without metastasis (p=0.05 and p=0.02, respectively). ROC curve analysis of thyroglobulin and RANKL expression resulted in the optimal cutoff value of both parameters. Thyroglobulin cutoff value was 1.70 and RANKL cutoff value was 1.95. The analysis showed significant correlation between high expression of thyroglobulin with the incidence of bony metastasis (p=0.044). Similar result was also found in the high expression of RANKL (p=0.02).Conclusions: Increased thyroglobulin and RANKL expression are a risk factor of bone metastasis on patients with thyroid cancer.

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