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Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway

Authors
Kim, So-YeonOh, YounseoJo, SungsinJi, Jong-DaeKim, Tae-Hwan
Issue Date
12월-2021
Publisher
MDPI
Keywords
aryl-hydrocarbon receptor; bone remodeling; kynurenine; osteoclast; osteoclastogenesis; rheumatoid arthritis
Citation
CELLS, v.10, no.12
Indexed
SCIE
SCOPUS
Journal Title
CELLS
Volume
10
Number
12
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/135646
DOI
10.3390/cells10123498
ISSN
2073-4409
Abstract
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).
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