title: Aryl hydrocarbon receptor catabolic activity in bone metabolism is osteoclast dependent in vivo.
abstract: Bone mass is regulated by various molecules including endogenous factors as well as exogenous factors, such as nutrients and pollutants. Aryl hydrocarbon receptor (AhR) is known as a dioxin receptor and is responsible for various pathological and physiological processes. However, the role of AhR in bone homeostasis remains elusive because the cell type specific direct function of AhR has never been explored in vivo. Here, we show the cell type specific function of AhR in vivo in bone homeostasis. Systemic AhR knockout (AhRKO) mice exhibit increased bone mass with decreased resorption and decreased formation. Meanwhile, osteoclast specific AhRKO (AhR(ΔOc/ΔOc)) mice have increased bone mass with reduced bone resorption, although the mice lacking AhR in osteoblasts have a normal bone phenotype. Even under pathological conditions, AhR(ΔOc/ΔOc) mice are resistant to sex hormone deficiency-induced bone loss resulting from increased bone resorption. Furthermore, 3-methylcholanthrene, an AhR agonist, induces low bone mass with increased bone resorption in control mice, but not in AhR(ΔOc/ΔOc) mice. Taken together, cell type specific in vivo evidence for AhR functions indicates that osteoclastic AhR plays a significant role in maintenance of bone homeostasis, suggesting that inhibition of AhR in osteoclasts can be beneficial in the treatment of osteoporosis.
authors.affiliation: Division of Integrative Pathophysiology, Proteo-Science Center, Graduate School of Medicine, Ehime University, Ehime 791-0295, Japan; Laboratory of Epigenetic Skeletal Diseases, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Tai-yong
authors.initials: TY
authors.lastname: Yu
authors.affiliation: Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.affiliation: Division of Integrative Pathophysiology, Proteo-Science Center, Graduate School of Medicine, Ehime University, Ehime 791-0295, Japan; Laboratory of Epigenetic Skeletal Diseases, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: y-imai@m.ehime-u.ac.jp.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008660:Metabolism; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D010052:Ovariectomy; D011859:Radiography; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D018336:Receptors, Aryl Hydrocarbon
keywords: Aryl hydrocarbon receptor (AhR); Bone; Osteoclast