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Article

4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model

by 1,†, 2,†, 3 and 1,*
1
Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 11490, Taiwan
2
Department of Anesthesiology, Cheng-Hsin General Hospital, Taipei 11220, Taiwan
3
School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(18), 6971; https://doi.org/10.3390/ijms21186971
Received: 26 August 2020 / Revised: 16 September 2020 / Accepted: 18 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue Disease, Ageing and Cancer Prevention by Natural Products)
Astronauts suffer from 1–2% bone loss per month during space missions. Targeting osteoclast differentiation has been regarded as a promising strategy to prevent osteoporosis in microgravity (μXg). 4-acetylantroquinonol B (4-AAQB), a ubiquinone from Antrodia cinnamomea, has shown anti-inflammatory and anti-hepatoma activities. However, the effect of 4-AAQB on μXg-induced osteoclastogenesis remains unclear. In this study, we aimed to explore the mechanistic impact of 4-AAQB on osteoclast formation under μXg conditions. The monocyte/macrophage-like cell line RAW264.7 was exposed to simulated μXg (Rotary Cell Culture System; Synthecon, Houston, TX, USA) for 24 h and then treated with 4-AAQB or alendronate (ALN) and osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclastogenesis, bone resorption activity, and osteoclast differentiation-related signaling pathways were analyzed using tartrate-resistant acid phosphatase (TRAP) staining, actin ring fluorescent staining, bone resorption, and western blotting assays. Based on the results of TRAP staining, actin ring staining, and bone resorption assays, we found that 4-AAQB significantly inhibited μXg-induced osteoclast differentiation. The critical regulators of osteoclast differentiation, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, and dendritic cell-specific transmembrane protein (DC-STAMP), were consistently decreased. Meanwhile, osteoclast apoptosis and cell cycle arrest were also observed along with autophagy suppression. Interestingly, the autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) showed similar effects to 4-AAQB. In conclusion, we suggest that 4-AAQB may serve as a potential agent against μXg-induced osteoclast formation. View Full-Text
Keywords: 4-acetylantroquinonol B; microgravity; osteoclastogenesis; autophagy 4-acetylantroquinonol B; microgravity; osteoclastogenesis; autophagy
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MDPI and ACS Style

Wu, C.-H.; Ou, C.-H.; Yen, I.-C.; Lee, S.-Y. 4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model. Int. J. Mol. Sci. 2020, 21, 6971. https://doi.org/10.3390/ijms21186971

AMA Style

Wu C-H, Ou C-H, Yen I-C, Lee S-Y. 4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model. International Journal of Molecular Sciences. 2020; 21(18):6971. https://doi.org/10.3390/ijms21186971

Chicago/Turabian Style

Wu, Chia-Hsin, Ching-Huei Ou, I-Chuan Yen, and Shih-Yu Lee. 2020. "4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model" International Journal of Molecular Sciences 21, no. 18: 6971. https://doi.org/10.3390/ijms21186971

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