2. Academic Validation
  3. 8-Nitro-cGMP is a promoter of osteoclast differentiation induced by RANKL

8-Nitro-cGMP is a promoter of osteoclast differentiation induced by RANKL

  • Nitric Oxide. 2018 Jan 30:72:46-51. doi: 10.1016/j.niox.2017.11.006.
K Kaneko 1,  Y Miyamoto 2,  R Tsukuura 1,  K Sasa 3,  T Akaike 4,  S Fujii 4,  K Yoshimura 3,  K Nagayama 5,  M Hoshino 6,  S Inoue 6,  K Maki 7,  K Baba 6,  D Chikazu 8,  R Kamijo 3
Affiliations

Affiliations

  • 1 Department of Biochemistry, Showa University School of Dentistry, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Japan.
  • 2 Department of Biochemistry, Showa University School of Dentistry, Japan. Electronic address: yoichim@dent.showa-u.ac.jp.
  • 3 Department of Biochemistry, Showa University School of Dentistry, Japan.
  • 4 Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Japan.
  • 5 Department of Biochemistry, Showa University School of Dentistry, Japan; Department of Orthodontics, Showa University School of Dentistry, Japan.
  • 6 Department of Prosthodontics, Showa University School of Dentistry, Japan.
  • 7 Department of Orthodontics, Showa University School of Dentistry, Japan.
  • 8 Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Japan.
PMID: 29183803 DOI: 10.1016/j.niox.2017.11.006
Abstract

Osteoclasts are multinucleated giant cells differentiated from monocyte-macrophage-lineage cells under stimulation of receptor activator of nuclear factor κ-B (RANK) ligand (RANKL) produced by osteoblasts and osteocytes. Although it has been reported that nitric oxide (NO) and Reactive Oxygen Species (ROS) are involved in this process, the mechanism by which these labile molecules promote osteoclast differentiation are not fully understood. In this study, we investigated the formation and function of 8-nitro-cGMP, a downstream molecule of NO and ROS, in the process of osteoclast differentiation in vitro. 8-Nitro-cGMP was detected in mouse bone marrow macrophages and osteoclasts differentiated from macrophages in the presence of RANKL. Inhibition of NO Synthase suppressed the formation of 8-nitro-cGMP as well as RANKL-induced osteoclast differentiation from macrophages. On the Other hand, RANKL-induced osteoclast differentiation was promoted by addition of 8-nitro-cGMP to the cultures. In addition, 8-nitro-cGMP enhanced the mRNA expression of RANK, the receptor for RANKL. However, 8-bromo-cGMP, a membrane-permeable derivative of cGMP, did not have an effect on either RANKL-induced osteoclast differentiation or expression of the RANK gene. These results suggest that 8-nitro-cGMP is a novel positive regulator of osteoclast differentiation, which might help to explain the roles of NO and ROS in osteoclast differentiation.

Keywords

8-Nitro-cGMP; Nitric oxide; Osteoclasts; Reactive oxygen species.

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