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[논문] Bisphenol A inhibits osteogenic activity and causes bone resorption via the activation of retinoic acid-related orphan receptor α

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논문제목(Title)

[논문] Bisphenol A inhibits osteogenic activity and causes bone resorption via the activation of retinoic acid-related orphan receptor α

학술지명(Journal)

Journal of Hazardous Materials

ImpactFactor

14.224

ISSN_ISBN

0304-3894

학술지볼륨권호(Volume)

438

SCI구분

SCIE

초록(Abstract)

Bisphenol A (BPA) has deleterious effects on bone metabolism; however, its underlying mechanism has not yet been comprehensively understood. Here, we investigated whether RORα plays an important role in BPA-induced bone resorption both in vitro and in vivo. We found that BPA (0.1–1 μM) inhibited osteogenic activity (including ALP activity and mineralization), decreased the expression levels of osteoblast markers (such as RUNX2, OSX, and ALP) in human MG-63 osteoblast-like osteosarcoma cells, and inhibited spontaneous vertebral formation in zebrafish larvae. Additionally, BPA diminished β-glycerophosphate-induced osteoblast differentiation and vertebral formation, while simultaneously downregulating the expression levels of RUNX2a, OSX, and ALP. Furthermore, molecular docking data showed that a hydroxyl group of BPA dominantly binds to the H3 (ALA70) and/or H5 (ARG107) of RORα-ligand binding domain with hydrogen bonding (ALA330 and/or ARG367 in the full length of RORα, respectively), which another hydroxyl group of BPA fits into H3, H6, and H7 elements with non-covalent interactions, resulting in the activation of RORα. However, an RORα inverse agonist potently inhibited BPA-induced anti-osteogenic activity and vertebral formation in zebrafish larvae, concomitant with inhibition of osteogenic gene expression. Overall, our findings reveal that BPA inhibits osteoblast differentiation and bone formation by activating RORα. These results suggest that BPA exposure (0.1–1 μM) can cause various bone-resorptive diseases, such as osteoporosis.

저자명(Author)

Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Yung Hyun Choi, Sang Rul Park, Chang-Min Lee, Gi-Young Kim

학술지출판일자(PublicationDate)

2022.6.26.

DMP

연구책임자 / 소속

김기영

당해연구기간

2022.03.01-2023.02.28

공개 및 라이선스

공개 일자

2023-01-07

라이선스

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이 데이터의 저작권은 <연구자 기관/그룹/사용자>에게 있습니다.

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컬렉션
[김기영] Bisphenol A의 골(뼈)대사 교란에 미치는 영향 (2022)
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공개일자
2023-01-07
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  • Version 1 2023-01-04
Cite as
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Yung Hyun Choi, Sang Rul Park, Chang-Min Lee, Gi-Young Kim, 2022.6.26., [논문] Bisphenol A inhibits osteogenic activity and causes bone resorption via the activation of retinoic acid-related orphan receptor α
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