Reactive oxygen species mediate RANK signaling in osteoclasts

Ha, Hyunil; Kwak, Han Bok; Lee, Soo Woong; Jin, Hye-Mi; Kim, Hyun‐Man; Kim, Hong-Hee; Lee, Zang Hee

doi:10.1016/j.yexcr.2004.07.035

Cited by 307 publications

(257 citation statements)

References 45 publications

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“…This is supported by the observations that addition of exogenous hydrogen peroxide stimulates osteoclastic bone resorption and cell motility (26). Alternatively, antioxidants can block the RANKL-dependent signaling (27,28).…”

Section: Discussionmentioning

confidence: 81%

NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts

et al. 2009

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Section: Discussionmentioning

confidence: 81%

NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts

et al. 2009

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“…This result indicates that nano-Pt do not delay, but inhibit, osteoclast differentiation and fusion (13,15).…”

Section: Discussionmentioning

confidence: 89%

“…In addition, a recent study indicated that N-acetylcysteine, a chemical oxidant scavenger, blocks RANKLinduced ROS production and osteoclastogenesis (13). These reports suggested that ROS are essential for the formation and function of osteoclasts and regulate RANKL-stimulated osteoclast differentiation (13,15).…”

Section: Introductionmentioning

confidence: 99%

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

et al. 2011

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Abstract.Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-κB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre-osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS-scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOXfamily oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano-Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases.

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“…Binding of RANKL to its cognant receptor on osteoclast precursors leads to activation of NF-κB that is required for osteoclast differentiation [19,20]. Reactive oxygen species (ROS) are also crucial for RANKL-induced osteoclastogenesis [21][22][23][24] and NF-κB is among the redoxsensitive cell signaling pathways [25][26][27]. Recent studies indicate that ROS such as hydrogen peroxide produced in BMM cells stimulate osteoclast differentiation, whereas decreasing the level of ROS reverses RANKL responses [28].…”

Section: Introductionmentioning

confidence: 99%

High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis

Wittrant

Gorin

Woodruff

et al. 2008

Bone

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Diabetes is a chronic disease associated with hyperglycemia and altered bone metabolism that may lead to complications including osteopenia, increased risk of fracture and osteoporosis. Hyperglycemia has been implicated in the pathogenesis of diabetic bone disease; however, the biologic effect of glucose on osteoclastogenesis is unclear. In the present study, we examined the effect of high D(+)glucose (D-Glc) and L(−)glucose (L-Glc; osmotic control) on RANKL-induced osteoclastogenesis using RAW264.7 cells and Bone Marrow Macrophages (BMM) as models. Cells were exposed to sustained high glucose levels to mimic diabetic conditions. Osteoclast formation was analyzed using tartrate resistant acid phosphatase (TRACP) assay, expression of calcitonin receptor (CTR) and cathepsin K mRNAs, and cultures were examined for reactive oxygen species (ROS) using dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence, caspase-3 and Nuclear Factor kappaB (NF-κB) activity. Cellular function was assessed using a migration assay. Results show, for the first time, that high D-Glc inhibits osteoclast formation, ROS production, caspase-3 activity and migration in response to RANKL through a metabolic pathway. Our findings also suggest that high D-Glc may alter RANKL-induced osteoclast formation by inhibiting redox-sensitive NF-κB activity through an anti-oxidative mechanism. This study increases our understanding of the role of glucose in diabetes-associated bone disease. Our data suggest that high glucose levels may alter bone turnover by decreasing osteoclast differentiation and function in diabetes and provide new insight into the biologic effects of glucose on osteoclastogenesis.

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Reactive oxygen species mediate RANK signaling in osteoclasts

Cited by 307 publications

References 45 publications

NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts

NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis

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