Role of NF-κB in the skeleton

Novack, Deborah V.

doi:10.1038/cr.2010.159

Cited by 267 publications

(266 citation statements)

References 103 publications

(118 reference statements)

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“…[35][36][37] Genetic mouse models revealed that NIK is required for the proper development and/or maintenance of secondary lymphoid organs, for osteoclastogenesis, for T-cell activation as well for B-cell survival. 35,38,39 In this paper, we highlight an unexpected role for NIK in TNFR1-induced cell death. We found that NIK diverges from the alternative NF-κB pathway to promote cell death.…”

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confidence: 91%

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

et al. 2015

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NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway. Here we reveal an unexpected new role of NIK in TNFR1-mediated RIP1-dependent apoptosis, a consequence of TNFR1 activation observed in c-IAP1/2-depleted conditions. We show that NIK stabilization, obtained by activation of the non-death TNFRs Fn14 or LTβR, is required for TNFα-mediated apoptosis. These apoptotic stimuli trigger the depletion of c-IAP1/2, the phosphorylation of RIP1 and the RIP1 kinase-dependent assembly of the RIP1/FADD/caspase-8 complex.In the absence of NIK, the phosphorylation of RIP1 and the formation of RIP1/FADD/caspase-8 complex are compromised while c-IAP1/2 depletion is unaffected. In vitro kinase assays revealed that recombinant RIP1 is a bona fide substrate of NIK. In vivo, we demonstrated the requirement of NIK pro-death function, but not the processing of its substrate p100 into p52, in a mouse model of TNFR1/LTβR-induced thymus involution. In addition, we also highlight a role for NIK in hepatocyte apoptosis in a mouse model of virus-induced TNFR1/RIP1-dependent liver damage. We conclude that NIK not only contributes to lymphoid organogenesis, inflammation and cell survival but also to TNFR1/RIP1-dependent cell death independently of the alternative NF-κB pathway.

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confidence: 91%

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

et al. 2015

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“…Osteoclasts, originate from hematopoietic progenitors, are essential for bone homeostasis, and play a vital role in both the development of osteoporosis and the metastasis of tumors to bone. The formation of osteoclasts involves several factors such as receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) and macrophage colony-stimulating factor (Novack, 2011). Many researchers have shown that RANKL is directly involved in the differentiation of macrophages into osteoclasts (Wang et al, 2003;Kukita and Kukita, 2013).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of andrographolide in RAW 264.7 murine macrophage osteoclastogenesis by downregulating the nuclear factor-kappaB signaling pathway

Ren

Yuan

2015

Genet. Mol. Res.

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ABSTRACT. This study aims to investigate the effects of andrographolide (AGP) on osteoclast formation in RAW 264.7 murine macrophage cells. The effects of AGP on cell viability were determined in RAW 264.7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of AGP on osteoclast formation were tested by osteoclast staining with tartrate-resistant acid phosphatase (TRAP). The effects of AGP on receptor activator of nuclear factor-kappaB (NFkappaB) ligand (RANKL)-induced, NF-kappaB-dependent transcription in RAW 264.7 cells were assessed using luciferase reporter assays. The results demonstrated that the viability of osteoclast precursor RAW 264.7 cells was not affected by AGP treatment at a concentration of 0.4 to 10 μM. Additionally, the number of TRAP-positive osteoclasts was significantly reduced by the same concentrations of AGP treatment. AGP also inhibited RANKL-induced NF-kappaB activation in a dose-dependent 15955-15961 (2015) fashion as evidenced by luciferase reporter assays. In summary, this study demonstrates that AGP inhibits osteoclastogenesis in RAW 264.7 murine macrophage cells through downregulation of the NF-kappaB signaling pathway.

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“…Receptor activator of nuclear factor kappa-B ligand was reported to be the unique osteoclastogenesis cytokine promoting osteoclast formation (17,18,43). It has been suggested that osteoclast functional activity rather than formation is increased in primary osteoporosis and that dexamethasone acts to increase osteoclast formation (15).…”

Section: Discussionmentioning

confidence: 99%

“…Data were collected using the following tools: Receptor activator of nuclear factor kappa-B ligand is a tumour necrosis factor (TNF) family member produced and secreted by osteoblasts, which, through binding to its receptor (RANK) on progenitor and mature osteoclasts, regulates osteoclastogenesis and activation of osteoclasts in normal and pathological states of bone remodelling (17,18). Osteoprotegerin is a "protector of the bone" TNF receptor family member produced by osteoblasts that binds to RANKL and thereby blocks the RANKL-RANK interaction, inhibiting differentiation and activation of the osteoclasts (19), as illustrated in Fig.…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

Parallel Assessment of Bone Mineral Density and RANKL/OPG Ratio in Saudi Females

Hassan¹,

Eltarhouny²,

Hashem³

et al. 2015

WIMJ Open

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Role of NF-κB in the skeleton

Cited by 267 publications

References 103 publications

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

Inhibition of andrographolide in RAW 264.7 murine macrophage osteoclastogenesis by downregulating the nuclear factor-kappaB signaling pathway

Parallel Assessment of Bone Mineral Density and RANKL/OPG Ratio in Saudi Females

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