title: Aryl hydrocarbon receptors in osteoclast lineage cells are a negative regulator of bone mass.
abstract: Aryl hydrocarbon receptors (AhRs) play a critical role in various pathological and physiological processes. Although recent research has identified AhRs as a key contributor to bone metabolism following studies in systemic AhR knockout (KO) or transgenic mice, the cellular and molecular mechanism(s) in this process remain unclear. In this study, we explored the function of AhR in bone metabolism using AhR(RANKΔOc/ΔOc) (RANK(Cre/+);AhR(flox/flox)) mice. We observed enhanced bone mass together with decreased resorption in both male and female 12 and 24-week-old AhR(RANKΔOc/ΔOc) mice. Control mice treated with 3-methylcholanthrene (3MC), an AhR agonist, exhibited decreased bone mass and increased bone resorption, whereas AhR(CtskΔOc/ΔOc) (Ctsk(Cre/+);AhR(flox/flox)) mice injected with 3MC appeared to have a normal bone phenotype. In vitro, bone marrow-derived macrophages (BMDMs) from AhR(RANKΔOc/ΔOc) mice exhibited impaired osteoclastogenesis and repressed differentiation with downregulated expression of B lymphocyte-induced maturation protein 1 (Blimp1), and cytochrome P450 genes Cyp1b1 and Cyp1a2. Collectively, our results not only demonstrated that AhR in osteoclast lineage cells is a physiologically relevant regulator of bone resorption, but also highlighted the need for further studies on the skeletal actions of AhR inhibitors in osteoclast lineage cells commonly associated with bone diseases, especially diseases linked to environmental pollutants known to induce bone loss.
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: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi Province, 712100, P.R. China.
authors.forename: Wei-jun
authors.initials: WJ
authors.lastname: Pang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi Province, 712100, P.R. China.
authors.forename: Gong-she
authors.initials: GS
authors.lastname: Yang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D015519:Bone Density; D001862:Bone Resorption; D002478:Cells, Cultured; D005260:Female; D005269:Femur / Q000502:physiology*; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse