scholarly journals Dual Oxidase Maturation Factor 1 Positively Regulates RANKL-Induced Osteoclastogenesis via Activating Reactive Oxygen Species and TRAF6-Mediated Signaling

2020 ◽  
Vol 21 (17) ◽  
pp. 6416
Author(s):  
Yoon-Hee Cheon ◽  
Chang Hoon Lee ◽  
Da Hye Jeong ◽  
Sung Chul Kwak ◽  
Soojin Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Osteoclast Differentiation ◽  
Tumor Necrosis Factor Receptor ◽  
Reactive Oxygen ◽  
Osteoclast Formation ◽  
Ros Production ◽  
Oxygen Species ◽  
Maturation Factor ◽  
Dual Oxidase ◽  
Rankl Stimulation

Receptor activator of NF-κB ligand (RANKL) induces generation of intracellular reactive oxygen species (ROS), which act as second messengers in RANKL-mediated osteoclastogenesis. Dual oxidase maturation factor 1 (Duoxa1) has been associated with the maturation of ROS-generating enzymes including dual oxidases (Duox1 and Duox2). In the progression of osteoclast differentiation, we identified that only Duoxa1 showed an effective change upon RANKL stimulation, but not Duox1, Duox2, and Duoxa2. Therefore, we hypothesized that Duoxa1 could independently act as a second messenger for RANKL stimulation and regulate ROS production during osteoclastogenesis. Duoxa1 gradually increased during RANKL-induced osteoclastogenesis. Using siRNA or retrovirus transduction, we found that Duoxa1 regulated RANKL-stimulated osteoclast formation and bone resorption positively. Furthermore, knockdown of Duoxa1 decreased the RANKL-induced ROS production. During Duoxa1-related control of osteoclastogenesis, activation of tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated early signaling molecules including MAPKs, Akt, IκB, Btk, Src and PLCγ2 was affected, which sequentially modified the mRNA or protein expression levels of key transcription factors in osteoclast differentiation, such as c-Fos and NFATc1, as well as mRNA expression of osteoclast-specific markers. Overall, our data indicate that Duoxa1 plays a crucial role in osteoclastogenesis via regulating RANKL-induced intracellular ROS production and activating TRAF6-mediated signaling.

scholarly journals FRI0370 DUAL OXIDASE MATURATION FACTOR 1 POSITIVELY REGULATES RANKL-INDUCED OSTEOCLASTOGENESIS VIA ACTIVATING REACTIVE OXYGEN SPECIES PRODUCTION AND TRAF6-MEDIATED SIGNALING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 782.2-782
Author(s):  
C. H. Lee ◽  
C. H. Chung ◽  
Y. J. Choi ◽  
W. H. Yoo ◽  
J. Y. Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Osteoclast Differentiation ◽  
Reactive Oxygen ◽  
Mouse Bone Marrow ◽  
Ros Production ◽  
Oxygen Species ◽  
Maturation Factor ◽  
Intracellular Ros ◽  
Dual Oxidase ◽  
Rankl Stimulation

Background:Reactive oxygen species (ROS) are one of the significant factors of chemical or physical cell signaling in a wide variety of cell types including skeletal cells. Receptor activator of NF-βB ligand (RANKL) induces generation of intracellular ROS, which act as second messengers in RANKL-mediated osteoclastogenesis. Dual oxidase maturation factor 1 (Duoxa1) was first identified as aDrosophilaNumb-interacting protein (NIP), and has been associated with the maturation of ROS generating enzymes including dual oxidases (Duox1 and Duox2). In the progression of osteoclast differentiation using mouse bone marrow-derived macrophages (BMMs), we identified that only Duoxa1 level showed an effective change upon RANKL stimulation, but not Duox1, Duox2, and Duoxa2.Objectives:we hypothesized that Duoxa1 could independently act as a second messenger for RANKL stimulation and regulate ROS production during osteoclast differentiation.Methods:Using siRNA or retrovirus transduction and knockdown of Duoxa1 via siRNAResults:Duoxa1 level gradually increased during RANKL-induced osteoclast differentiation. We found that Duoxa1 regulated RANKL-stimulated osteoclast formation and bone resorption positively. knockdown of Duoxa1 via siRNA decreased the RANKL-induced ROS production. During Duoxa1-related control of osteoclastogenesis, activation of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediated early signaling molecules including MAPKs, Akt, IβB, Btk, and PLC 2 was affected, which sequentially modified the mRNA or protein expression levels of key transcription factors in osteoclastogenesis, such as c-Fos and NFATc1, as well as mRNA expression of osteoclast-specific markers including OSCAR, ATP6v0d2, and CtsK.Conclusion:Overall, our data indicate that Duoxa1 plays a crucial role in osteoclastogenesis via regulating RANKL-induced intracellular ROS production and activating TRAF6-mediated signaling.Disclosure of Interests:None declared

A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 852-859 ◽  
Author(s):  
Na Kyung Lee ◽  
Young Geum Choi ◽  
Ji Youn Baik ◽  
Song Yi Han ◽  
Dae-won Jeong ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Osteoclast Differentiation ◽  
Tumor Necrosis Factor Receptor ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Ros Production ◽  
Oxygen Species ◽  
Diphenylene Iodonium

Abstract Signaling by receptor activator of NF-κB (nuclear factor-κB) ligand (RANKL) is essential for differentiation of bone marrow monocyte-macrophage lineage (BMM) cells into osteoclasts. Here, we show RANKL stimulation of BMM cells transiently increased the intracellular level of reactive oxygen species (ROS) through a signaling cascade involving TNF (tumor necrosis factor) receptor-associated factor (TRAF) 6, Rac1, and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) 1. A deficiency in TRAF6 or expression of a dominant-interfering mutant of TRAF6 blocks RANKL-mediated ROS production. Application of N-acetylcysteine (NAC) or blocking the activity of Nox, a protein leading to the formation of ROS, with diphenylene iodonium (DPI) inhibits the responses of BMM cells to RANKL, including ROS production, activation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK), and osteoclast differentiation. Moreover, both RANKL-mediated ROS production and osteoclast differentiation were completely blocked in precursors depleted of Nox1 activity by RNA interference or by expressing a dominant-negative mutant of Rac1. Together, these results indicate that ROSs act as an intracellular signal mediator for osteoclast differentiation.

scholarly journals GPR120 Inhibits RANKL-Induced Osteoclast Formation and Resorption by Attenuating Reactive Oxygen Species Production in RAW264.7 Murine Macrophages

2021 ◽  
Vol 22 (19) ◽  
pp. 10544
Author(s):  
Cynthia Sithole ◽  
Carla Pieterse ◽  
Kayla Howard ◽  
Abe Kasonga
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Ros Production ◽  
Oxygen Species ◽  
Murine Macrophages ◽  
Multinucleated Cells ◽  
Raw264.7 Macrophages ◽  
Inhibit Osteoclast Formation

Osteoclasts are large, multinucleated cells that are responsible for the resorption of bone. Bone degenerative diseases, such as osteoporosis, are characterized by overactive osteoclasts. Receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) binding to its receptor on osteoclast precursors will trigger osteoclast formation and resorption. The production of reactive oxygen species (ROS) is known to play a crucial role in RANKL-induced osteoclast formation and resorption. G-protein coupled receptor 120 (GPR120) signalling has been shown to affect osteoclast formation, but the exact mechanisms of action require further investigation. RAW264.7 murine macrophages were seeded into culture plates and exposed to the GPR120 agonist, TUG-891, at varying concentrations (20–100 µM) and RANKL to induce osteoclast formation. TUG-891 was shown to inhibit osteoclast formation and resorption without affecting cell viability in RAW264.7 macrophages. TUG-891 further decreased ROS production when compared to RANKL only cells. Antioxidant proteins, Nrf2, HO-1 and NQO1 were shown to be upregulated while the ROS inducing protein, Nox1, was downregulated by TUG-891. Gene silencing revealed that TUG-891 exerted its effects specifically through GPR120. This study reveals that GPR120 signalling may inhibit osteoclast formation and resorption through inhibition on ROS production.

scholarly journals Reactive Oxygen Species in Host Plant Are Required for an Early Defense Response against Attack of Stagonospora nodorum Berk. Necrotrophic Effectors SnTox

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1586
Author(s):  
Svetlana Veselova ◽  
Tatyana Nuzhnaya ◽  
Guzel Burkhanova ◽  
Sergey Rumyantsev ◽  
Igor Maksimov
Keyword(s):  
Reactive Oxygen Species ◽  
Early Stage ◽  
Reactive Oxygen ◽  
Triticum Aestivum L ◽  
Redox Status ◽  
Stagonospora Nodorum ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotrophic Effectors

Reactive oxygen species (ROS) play a central role in plant immune responses. The most important virulence factors of the Stagonospora nodorum Berk. are multiple fungal necrotrophic effectors (NEs) (SnTox) that affect the redox-status and cause necrosis and/or chlorosis in wheat lines possessing dominant susceptibility genes (Snn). However, the effect of NEs on ROS generation at the early stages of infection has not been studied. We studied the early stage of infection of various wheat genotypes with S nodorum isolates -Sn4VD, SnB, and Sn9MN, carrying a different set of NE genes. Our results indicate that all three NEs of SnToxA, SnTox1, SnTox3 significantly contributed to cause disease, and the virulence of the isolates depended on their differential expression in plants (Triticum aestivum L.). The Tsn1–SnToxA, Snn1–SnTox1and Snn3–SnTox3 interactions played an important role in inhibition ROS production at the initial stage of infection. The Snn3–SnTox3 inhibited ROS production in wheat by affecting NADPH-oxidases, peroxidases, superoxide dismutase and catalase. The Tsn1–SnToxA inhibited ROS production in wheat by affecting peroxidases and catalase. The Snn1–SnTox1 inhibited the production of ROS in wheat by mainly affecting a peroxidase. Collectively, these results show that the inverse gene-for gene interactions between effector of pathogen and product of host sensitivity gene suppress the host’s own PAMP-triggered immunity pathway, resulting in NE-triggered susceptibility (NETS). These results are fundamentally changing our understanding of the development of this economical important wheat disease.

scholarly journals Production and scavenging of reactive oxygen species both affect reproductive success in male and female Drosophila melanogaster

2021 ◽  
Author(s):  
Biz R. Turnell ◽  
Luisa Kumpitsch ◽  
Klaus Reinhardt
Keyword(s):  
Reactive Oxygen Species ◽  
Drosophila Melanogaster ◽  
Reactive Oxygen ◽  
Cellular Aging ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type ◽  
Ros Scavenging ◽  
Respiratory Pathway ◽  
Male And Female

AbstractSperm aging is accelerated by the buildup of reactive oxygen species (ROS), which cause oxidative damage to various cellular components. Aging can be slowed by limiting the production of mitochondrial ROS and by increasing the production of antioxidants, both of which can be generated in the sperm cell itself or in the surrounding somatic tissues of the male and female reproductive tracts. However, few studies have compared the separate contributions of ROS production and ROS scavenging to sperm aging, or to cellular aging in general. We measured reproductive fitness in two lines of Drosophila melanogaster genetically engineered to (1) produce fewer ROS via expression of alternative oxidase (AOX), an alternative respiratory pathway; or (2) scavenge fewer ROS due to a loss-of-function mutation in the antioxidant gene dj-1β. Wild-type females mated to AOX males had increased fecundity and longer fertility durations, consistent with slower aging in AOX sperm. Contrary to expectations, fitness was not reduced in wild-type females mated to dj-1β males. Fecundity and fertility duration were increased in AOX and decreased in dj-1β females, indicating that female ROS levels may affect aging rates in stored sperm and/or eggs. Finally, we found evidence that accelerated aging in dj-1β sperm may have selected for more frequent mating. Our results help to clarify the relative roles of ROS production and ROS scavenging in the male and female reproductive systems.

scholarly journals Reactive oxygen species rescue regeneration after silencing the MAPK–ERK signaling pathway in Schmidtea mediterranea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
V. Jaenen ◽  
S. Fraguas ◽  
K. Bijnens ◽  
M. Heleven ◽  
T. Artois ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Light Therapy ◽  
Erk Signaling ◽  
Model Organisms ◽  
Ros Production ◽  
Oxygen Species ◽  
Planarian Regeneration ◽  
Egfr Signaling Pathway

AbstractDespite extensive research on molecular pathways controlling the process of regeneration in model organisms, little is known about the actual initiation signals necessary to induce regeneration. Recently, the activation of ERK signaling has been shown to be required to initiate regeneration in planarians. However, how ERK signaling is activated remains unknown. Reactive Oxygen Species (ROS) are well-known early signals necessary for regeneration in several models, including planarians. Still, the probable interplay between ROS and MAPK/ERK has not yet been described. Here, by interfering with major mediators (ROS, EGFR and MAPK/ERK), we were able to identify wound-induced ROS, and specifically H2O2, as upstream cues in the activation of regeneration. Our data demonstrate new relationships between regeneration-related ROS production and MAPK/ERK activation at the earliest regeneration stages, as well as the involvement of the EGFR-signaling pathway. Our results suggest that (1) ROS and/or H2O2 have the potential to rescue regeneration after MEK-inhibition, either by H2O2-treatment or light therapy, (2) ROS and/or H2O2 are required for the activation of MAPK/ERK signaling pathway, (3) the EGFR pathway can mediate ROS production and the activation of MAPK/ERK during planarian regeneration.

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