Next Article in Journal
The Specific Mitogen- and Stress-Activated Protein Kinase MSK1 Inhibitor SB-747651A Modulates Chemokine-Induced Neutrophil Recruitment
Next Article in Special Issue
Thyroid Disrupting Chemicals
Previous Article in Journal
Human Chorionic Gonadotropin as a Pivotal Endocrine Immune Regulator Initiating and Preserving Fetal Tolerance
Previous Article in Special Issue
Interference of Paraben Compounds with Estrogen Metabolism by Inhibition of 17β-Hydroxysteroid Dehydrogenases
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(10), 2159; https://doi.org/10.3390/ijms18102159

Roles of Aryl Hydrocarbon Receptor in Aromatase-Dependent Cell Proliferation in Human Osteoblasts

1
Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDeS), Tohoku University, Sendai, Miyagi 980-8575, Japan
2
Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan
3
Department of Oral Pathology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, Japan
4
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan
*
Author to whom correspondence should be addressed.
Received: 9 October 2017 / Revised: 13 October 2017 / Accepted: 13 October 2017 / Published: 17 October 2017
(This article belongs to the Special Issue Advances in the Research of Endocrine Disrupting Chemicals)
Full-Text   |   PDF [2269 KB, uploaded 17 October 2017]   |  

Abstract

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and its expression is influenced by environmental compounds, such as 3-methylcholanthrene (3-MC) and β-naphthoflavone (β-NF). AhR and its downstream genes, such as CYP1A1, are considered to play a pivotal role in xenobiotic responses. AhR signaling has also been proposed to mediate osteogenesis in experimental animals, but its details have remained unclear. Therefore, in this study, we examined the possible roles of AhR in human bone. Immunohistochemical analysis revealed that AhR was detected in both osteoblasts and osteoclasts. We then screened AhR-target genes using a microarray analysis in human osteoblastic hFOB cells. Results of microarray and subsequent PCR analysis did reveal that estrogen metabolizing and synthesizing enzymes, such as CYP1B1 and aromatase, were increased by 3-MC in hFOB and osteosarcoma cell line, MG-63. The subsequent antibody cytokine analysis also demonstrated that interleukin-1β and -6 expression was increased by 3-MC and β-NF in hFOB cells and these interleukins were well known to induce aromatase. We then examined the cell proliferation rate of hFOB and MG-63 cells co-treated with 3-MC and testosterone as an aromatase substrate. The status of cell proliferation in both hFOB and MG-63 cells was stimulated by 3-MC and testosterone treatment, which was also inhibited by an estrogen blocker, aromatase inhibitor, or AhR antagonist. These findings indicated that AhR could regulate estrogen synthesis and metabolism in bone tissues through cytokine/aromatase signaling. View Full-Text
Keywords: aryl hydrocarbon receptor; aromatase; osteoblast aryl hydrocarbon receptor; aromatase; osteoblast
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Miki, Y.; Hata, S.; Ono, K.; Suzuki, T.; Ito, K.; Kumamoto, H.; Sasano, H. Roles of Aryl Hydrocarbon Receptor in Aromatase-Dependent Cell Proliferation in Human Osteoblasts. Int. J. Mol. Sci. 2017, 18, 2159.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top