title: Molecular regulatory mechanisms of osteoclastogenesis through cytoprotective enzymes.
abstract: It has been reported that reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, take part in osteoclast differentiation as intra-cellular signaling molecules. The current assumed signaling cascade from RANK to ROS production is RANK, TRAF6, Rac1, and then Nox. The target molecules of ROS in RANKL signaling remain unclear; however, several reports support the theory that NF-κB signaling could be the crucial downstream signaling molecule of RANKL-mediated ROS signaling. Furthermore, ROS exert cytotoxic effects such as peroxidation of lipids and phospholipids and oxidative damage to proteins and DNA. Therefore, cells have several protective mechanisms against oxidative stressors that mainly induce cytoprotective enzymes and ROS scavenging. Three well-known mechanisms regulate cytoprotective enzymes including Nrf2-, FOXO-, and sirtuin-dependent mechanisms. Several reports have indicated a crosslink between FOXO- and sirtuin-dependent regulatory mechanisms. The agonists against the regulatory mechanisms are reported to induce these cytoprotective enzymes successfully. Some of them inhibit osteoclast differentiation and bone destruction via attenuation of intracellular ROS signaling. In this review article, we discuss the above topics and summarize the current information available on the relationship between cytoprotective enzymes and osteoclastogenesis.
authors.affiliation: Tohoku University Hospital, Maxillo-Oral Disorders, Japan; Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan. Electronic address: kanzaki-h@tsurumi-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanzaki
authors.affiliation: Tohoku University Graduate School of Dentistry, Oral Microbiology, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shinohara
authors.affiliation: Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan.
authors.forename: Itohiya
authors.initials: I
authors.lastname: Kanako
authors.affiliation: Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan.
authors.forename: Sari
authors.initials: S
authors.lastname: Fukaya
authors.affiliation: Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wada
authors.affiliation: Department of orthodontics, School of Dental Medicine, Tsurumi University, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics
chemical_list: D000071161:Forkhead Box Protein O1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D053246:Receptor Activator of Nuclear Factor-kappa B; D051547:Heme Oxygenase-1; D037761:Sirtuins
keywords: FOXO; Heme-oxygenase 1 (HO-1); Nrf2; Osteoclast; Oxidative stress; Sirtuin