Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells
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DOI：
10.1254/jphs.11099fp
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发表时间：
2011-12-01
影响因子：
3.5
通讯作者：
Inoue, Nobuo
中科院分区：
文献类型：
--
作者：
Nomura, Mayumi;Yoshimura, Yoshitaka;Inoue, Nobuo
最近的研究表明，铂纳米颗粒（nano-Pt）作为还原催化剂可有效淬灭活性氧（ROS）。 ROS 被认为可以调节 NF-κ B 配体受体激活剂 (RANKL) 刺激的破骨细胞分化。在本研究中，我们检查了铂纳米 Pt 对 RANKL 诱导的小鼠破骨细胞 RAW 264.7 细胞分化的直接影响。测量了纳米铂对破骨细胞数量的影响，并使用实时 PCR 测定了纳米铂对破骨细胞分化 mRNA 表达的影响。纳米铂似乎具有 ROS 清除活性。 Nano-Pt 以剂量依赖性方式减少破骨细胞（2+ 细胞核）和大破骨细胞（8+ 细胞核）的数量，而不影响细胞活力。此外，该药物还显着阻断 RANKL 诱导的破骨细胞分化基因（如 c-fms、NFATc 1、NFATc2 和 DC-STAMP）以及破骨细胞特异性标记基因（包括 MMP-9、Cath-K、CLC7、ATP6i、CTR 和 TRAP）的 mRNA 表达。尽管纳米铂减弱了产生 ROS 的 NOX 家族氧化酶 Nox1 和 Nox4 的表达，但它们上调了巨噬细胞中主要 Nox 酶 Nox2 的表达。这些发现表明纳米铂通过其 ROS 清除特性抑制 RANKL 刺激的破骨细胞分化。使用纳米铂作为 RANKL 产生的 ROS 清除剂可能是治疗骨疾病的一种新颖且创新的疗法。
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-kappa B 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, NFATc 1, 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.