title: 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 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.
authors.affiliation: Department of Gerodontology, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo 060-8586, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nomura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuiri
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Yumi
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Deyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Koshiro
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Sano
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Inoue
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010984:Platinum / Q000008:administration & dosage / Q000737:chemistry*; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D053245:RANK Ligand; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D010984:Platinum