scholarly journals Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo

Molecules ◽  
2016 ◽  
Vol 21 (3) ◽  
pp. 295 ◽  
Author(s):  
Jong Baek ◽  
Ju-Young Kim ◽  
Sung-Jun Ahn ◽  
Yoon-Hee Cheon ◽  
Miyoung Yang ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Nuclear Factor ◽  
Inhibitory Effects ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

scholarly journals NLRP12 provides a critical checkpoint for osteoclast differentiation

2015 ◽  
Vol 112 (33) ◽  
pp. 10455-10460 ◽  
Author(s):  
Jennifer L. Krauss ◽  
Rong Zeng ◽  
Cynthia L. Hickman-Brecks ◽  
Justin E. Wilson ◽  
Jenny P.-Y. Ting ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Osteoclast Differentiation ◽  
Disease Model ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Genetic Ablation ◽  
Nuclear Factor Kappa

The alternative or noncanonical nuclear factor kappa B (NF-κB) pathway regulates the osteoclast (OC) response to receptor activator of nuclear factor kappa B ligand (RANKL) and thus bone metabolism. Although several lines of evidence support the emerging concept that nucleotide-binding leucine-rich repeat and pyrin domain-containing receptor 12 (NLRP12) impedes alternative NF-κB activation in innate immune cells, a functional role for NLRP12 outside an inflammatory disease model has yet to be reported. Our study demonstrates that NLRP12 has a protective role in bone via suppression of alternative NF-κB–induced osteoclastogenesis and is down-modulated in response to osteoclastogenic stimuli. Here, we show that retroviral overexpression of NLRP12 suppressed RelB nuclear translocation and OC formation. Conversely, genetic ablation of NLRP12 promoted NIK stabilization, RelB nuclear translocation, and increased osteoclastogenesis in vitro. Using radiation chimeras, we demonstrated these in vitro observations dovetail with our in vivo findings that NLRP12 deficiency leads to enhanced OC numbers accompanied by a significant decline in bone mass under physiological conditions. Consistent with the basal bone phenotype, we also observed an enhanced osteolytic response following RANKL injection over the calvaria of NLRP12-deficient chimeric mice compared with wild-type control mice. Thus, modulation of NLRP12 levels controls alternative NF-κB signaling in OC precursors, altering bone homeostasis and osteolytic responses.

L-Tetrahydropalmatine Inhibits the Progression of Glioblastoma Tumor by Suppressing the Extracellular-Signal-Regulated Kinase/Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 164-171
Author(s):  
Feng Xue ◽  
Tingting Chen
Keyword(s):  
Glioblastoma Multiforme ◽  
Nuclear Factor Kappa B ◽  
Matrix Metalloproteinase 2 ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Extracellular Signal ◽  
Apoptosis Protein ◽  
Endothelial Growth Factor

Glioblastoma multiforme is the most common malignancy of central nervous system. Herein we have evaluated the effect of L-tetrahydropalmatine, an isoquinoline alkaloid, on the tumor growth both in vivo and in vitro using C6 glioblastoma multiforme cells and BALB/c mice injected subcutaneously with C6/luc2 cells. The results of these studies show that L-tetrahydropalmatine exhibited cytotoxic effect on C6 glioblastoma multiforme cells, suppressed nuclear factor-kappa B activity, suppressed the levels of tumor-linked proteins such as matrix metalloproteinase-2/9, Cyclin-D1, vascular endothelial growth factor, and X-linked inhibitor of apoptosis protein via ERK/nuclear factor-kappa B cascade. Further, L-tetrahydropalmatine inhibited the cell migration and invasion properties of C6 cells, and also suppressed the tumor weight and volume in mice. Immunohistochemical staining of tumor tissues suggested that L-tetrahydropalmatine inhibited the extracellular-signal-regulated kinase/nuclear factor-kappa B cascade and suppressed the levels of Cyclin-D1; matrix metalloproteinase-2/9; X-linked inhibitor of apoptosis protein; and vascular endothelial growth factor, and also the progression and growth of glioblastoma multiforme in mice. In summary, L-tetrahydropalmatine inhibits the ERK/nuclear factor-kappa B cascade, decreases the tumor volume, and inhibits the proteins responsible for tumor growth both in vivo and in vitro.

scholarly journals Fucoidan Prevents RANKL-Stimulated Osteoclastogenesis and LPS-Induced Inflammatory Bone Loss via Regulation of Akt/GSK3β/PTEN/NFATc1 Signaling Pathway and Calcineurin Activity

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 345 ◽  
Author(s):  
Sheng-Hua Lu ◽  
Yi-Jan Hsia ◽  
Kuang-Chung Shih ◽  
Tz-Chong Chou
Keyword(s):  
Bone Loss ◽  
Molecular Mechanisms ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Calcineurin Activity

Excessive osteoclast differentiation and/or function plays a pivotal role in the pathogenesis of bone diseases such as osteoporosis and rheumatoid arthritis. Here, we examined whether fucoidan, a sulfated polysaccharide present in brown algae, attenuates receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and lipopolysaccharide (LPS)-induced bone resorption in vivo, and investigated the molecular mechanisms involved. Our results indicated that fucoidan significantly inhibited osteoclast differentiation in RANKL-stimulated macrophages and the bone resorbing activity of osteoclasts. The effects of fucoidan may be mediated by regulation of Akt/GSK3β/PTEN signaling and suppression of the increase in intracellular Ca2+ level and calcineurin activity, thereby inhibiting the translocation of nuclear factor-activated T cells c1 (NFATc1) into the nucleus. However, fucoidan-mediated NFATc1 inactivation was greatly reversed by kenpaullone, a GSK3β inhibitor. In addition, using microcomputer tomography (micro-CT) scanning and bone histomorphometry, we found that fucoidan treatment markedly prevented LPS-induced bone erosion in mice. Collectively, we demonstrated that fucoidan was capable of inhibiting osteoclast differentiation and inflammatory bone loss, which may be modulated by regulation of Akt/GSK3β/PTEN/NFATc1 and Ca2+/calcineurin signaling cascades. These findings suggest that fucoidan may be a potential agent for the treatment of osteoclast-related bone diseases.

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