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

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  • Nomura Mayumi
    Department of Gerodontology, Hokkaido University Graduate School of Dental Medicine, Japan Department of Molecular Cell Pharmacology, Hokkaido University Graduate School of Dental Medicine, Japan
  • Yoshimura Yoshitaka
    Department of Molecular Cell Pharmacology, Hokkaido University Graduate School of Dental Medicine, Japan
  • Kikuiri Takashi
    Department of Pediatric Dentistry, Hokkaido University Graduate School of Dental Medicine, Japan
  • Hasegawa Tomokazu
    Department of Pediatric Dentistry, Faculty of Dentistry, Tokushima University, Japan
  • Taniguchi Yumi
    Department of Pediatric Dentistry, Hokkaido University Graduate School of Dental Medicine, Japan
  • Deyama Yoshiaki
    Department of Molecular Cell Pharmacology, Hokkaido University Graduate School of Dental Medicine, Japan
  • Koshiro Ken-ichi
    Department of Restorative Dentistry, Hokkaido University Graduate School of Dental Medicine, Japan
  • Sano Hidehiko
    Department of Restorative Dentistry, Hokkaido University Graduate School of Dental Medicine, Japan
  • Suzuki Kuniaki
    Department of Molecular Cell Pharmacology, Hokkaido University Graduate School of Dental Medicine, Japan
  • Inoue Nobuo
    Department of Gerodontology, Hokkaido University Graduate School of Dental Medicine, Japan

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  • Platinum nanoparticles suppress osteoclatogenesis through scavenging of reactive oxygen species produced in RAW264.7 cells

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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.

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