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

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...

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Main Authors: Mayumi Nomura, Yoshitaka Yoshimura, Takashi Kikuiri, Tomokazu Hasegawa, Yumi Taniguchi, Yoshiaki Deyama, Ken-ichi Koshiro, Hidehiko Sano, Kuniaki Suzuki, Nobuo Inoue
Format: Article
Language:English
Published: Elsevier 2011-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319306115
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author Mayumi Nomura
Yoshitaka Yoshimura
Takashi Kikuiri
Tomokazu Hasegawa
Yumi Taniguchi
Yoshiaki Deyama
Ken-ichi Koshiro
Hidehiko Sano
Kuniaki Suzuki
Nobuo Inoue
author_facet Mayumi Nomura
Yoshitaka Yoshimura
Takashi Kikuiri
Tomokazu Hasegawa
Yumi Taniguchi
Yoshiaki Deyama
Ken-ichi Koshiro
Hidehiko Sano
Kuniaki Suzuki
Nobuo Inoue
author_sort Mayumi Nomura
collection DOAJ
description 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 NOX-family 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. Keywords:: platinum nanoparticle, osteoclast, reactive oxygen species (ROS), NOX, RAW cell
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spelling doaj.art-54dc497ecc5a418a9b64da455f60b6e72022-12-22T02:00:18ZengElsevierJournal of Pharmacological Sciences1347-86132011-01-011174243252Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 CellsMayumi Nomura0Yoshitaka Yoshimura1Takashi Kikuiri2Tomokazu Hasegawa3Yumi Taniguchi4Yoshiaki Deyama5Ken-ichi Koshiro6Hidehiko Sano7Kuniaki Suzuki8Nobuo Inoue9Department of Gerodontology, Kita-ku, Sapporo 060-8586, Japan; Department of Molecular Cell Pharmacology, Kita-ku, Sapporo 060-8586, JapanDepartment of Molecular Cell Pharmacology, Kita-ku, Sapporo 060-8586, Japan; Corresponding author. yoshi@den.hokudai.ac.jpDepartment of Pediatric Dentistry, and Kita-ku, Sapporo 060-8586, JapanDepartment of Pediatric Dentistry, Faculty of Dentistry, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima 770-8504, JapanDepartment of Pediatric Dentistry, and Kita-ku, Sapporo 060-8586, JapanDepartment of Molecular Cell Pharmacology, Kita-ku, Sapporo 060-8586, JapanDepartment of Restorative Dentistry, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo 060-8586, JapanDepartment of Restorative Dentistry, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo 060-8586, JapanDepartment of Molecular Cell Pharmacology, Kita-ku, Sapporo 060-8586, JapanDepartment of Gerodontology, Kita-ku, Sapporo 060-8586, JapanAbstract.: 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 NOX-family 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. Keywords:: platinum nanoparticle, osteoclast, reactive oxygen species (ROS), NOX, RAW cellhttp://www.sciencedirect.com/science/article/pii/S1347861319306115
spellingShingle Mayumi Nomura
Yoshitaka Yoshimura
Takashi Kikuiri
Tomokazu Hasegawa
Yumi Taniguchi
Yoshiaki Deyama
Ken-ichi Koshiro
Hidehiko Sano
Kuniaki Suzuki
Nobuo Inoue
Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
Journal of Pharmacological Sciences
title Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
title_full Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
title_fullStr Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
title_full_unstemmed Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
title_short Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
title_sort platinum nanoparticles suppress osteoclastogenesis through scavenging of reactive oxygen species produced in raw264 7 cells
url http://www.sciencedirect.com/science/article/pii/S1347861319306115
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