Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway
Aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor and regulates differentiation and function of various immune cells such as dendritic cells, Th17, and regulatory T cells. In recent studies, it was reported that AhR is involved in bone remodeling through regulating both oste...
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MDPI AG
2021-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/12/3498 |
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| author | So-Yeon Kim Younseo Oh Sungsin Jo Jong-Dae Ji Tae-Hwan Kim |
| author_facet | So-Yeon Kim Younseo Oh Sungsin Jo Jong-Dae Ji Tae-Hwan Kim |
| author_sort | So-Yeon Kim |
| collection | DOAJ |
| description | Aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor and regulates differentiation and function of various immune cells such as dendritic cells, Th17, and regulatory T cells. In recent studies, it was reported that AhR is involved in bone remodeling through regulating both osteoblasts and osteoclasts. However, the roles and mechanisms of AhR activation in human osteoclasts remain unknown. Here we show that AhR is involved in human osteoclast differentiation. We found that AhR expressed highly in the early stage of osteoclastogenesis and decreased in mature osteoclasts. Kynurenine (Kyn), formylindolo[3,4-b] carbazole (FICZ), and benzopyrene (BaP), which are AhR agonists, inhibited osteoclast formation and Kyn suppressed osteoclast differentiation at an early stage. Furthermore, blockade of AhR signaling through CH223191, an AhR antagonist, and knockdown of AhR expression reversed Kyn-induced inhibition of osteoclast differentiation. Overall, our study is the first report that AhR negatively regulates human osteoclast differentiation and suggests that AhR could be good therapeutic molecule to prevent bone destruction in chronic inflammatory diseases such as rheumatoid arthritis (RA). |
| first_indexed | 2024-03-10T04:25:57Z |
| format | Article |
| id | doaj.art-97d023f881da453388a36f1c01e9cd49 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:25:57Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-97d023f881da453388a36f1c01e9cd492023-11-23T07:38:35ZengMDPI AGCells2073-44092021-12-011012349810.3390/cells10123498Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor PathwaySo-Yeon Kim0Younseo Oh1Sungsin Jo2Jong-Dae Ji3Tae-Hwan Kim4Institute for Rheumatology Research, Hanyang University, Seoul 04763, KoreaInstitute for Rheumatology Research, Hanyang University, Seoul 04763, KoreaInstitute for Rheumatology Research, Hanyang University, Seoul 04763, KoreaDepartment of Rheumatology, College of Medicine, Korea University, Seoul 02841, KoreaInstitute for Rheumatology Research, Hanyang University, Seoul 04763, KoreaAryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor and regulates differentiation and function of various immune cells such as dendritic cells, Th17, and regulatory T cells. In recent studies, it was reported that AhR is involved in bone remodeling through regulating both osteoblasts and osteoclasts. However, the roles and mechanisms of AhR activation in human osteoclasts remain unknown. Here we show that AhR is involved in human osteoclast differentiation. We found that AhR expressed highly in the early stage of osteoclastogenesis and decreased in mature osteoclasts. Kynurenine (Kyn), formylindolo[3,4-b] carbazole (FICZ), and benzopyrene (BaP), which are AhR agonists, inhibited osteoclast formation and Kyn suppressed osteoclast differentiation at an early stage. Furthermore, blockade of AhR signaling through CH223191, an AhR antagonist, and knockdown of AhR expression reversed Kyn-induced inhibition of osteoclast differentiation. Overall, our study is the first report that AhR negatively regulates human osteoclast differentiation and suggests that AhR could be good therapeutic molecule to prevent bone destruction in chronic inflammatory diseases such as rheumatoid arthritis (RA).https://www.mdpi.com/2073-4409/10/12/3498aryl-hydrocarbon receptorosteoclastogenesisosteoclastbone remodelingkynureninerheumatoid arthritis |
| spellingShingle | So-Yeon Kim Younseo Oh Sungsin Jo Jong-Dae Ji Tae-Hwan Kim Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway Cells aryl-hydrocarbon receptor osteoclastogenesis osteoclast bone remodeling kynurenine rheumatoid arthritis |
| title | Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway |
| title_full | Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway |
| title_fullStr | Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway |
| title_full_unstemmed | Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway |
| title_short | Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway |
| title_sort | inhibition of human osteoclast differentiation by kynurenine through the aryl hydrocarbon receptor pathway |
| topic | aryl-hydrocarbon receptor osteoclastogenesis osteoclast bone remodeling kynurenine rheumatoid arthritis |
| url | https://www.mdpi.com/2073-4409/10/12/3498 |
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