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Article

Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression

by
Hyerim Lee
1,
Kyubin Lee
1,
Sheunghun Lee
1,
Jisu Lee
1,
Won Tae Jeong
2,
Heung Bin Lim
2,
Tae Kyung Hyun
2,
Sun-Ju Yi
1 and
Kyunghwan Kim
1,*
1
School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea
2
Department of Industrial Plant Science and Technology, Chungbuk National University, Cheongju 28644, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1347; https://doi.org/10.3390/ijms21041347
Submission received: 1 January 2020 / Revised: 8 February 2020 / Accepted: 14 February 2020 / Published: 17 February 2020
(This article belongs to the Section Bioactives and Nutraceuticals)
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Abstract

Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways in response to receptor activation of NF-κB ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development.
Keywords: Lentinula edodes; osteoclast; NFATc1; osteoporosis Lentinula edodes; osteoclast; NFATc1; osteoporosis

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MDPI and ACS Style

Lee, H.; Lee, K.; Lee, S.; Lee, J.; Jeong, W.T.; Lim, H.B.; Hyun, T.K.; Yi, S.-J.; Kim, K. Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression. Int. J. Mol. Sci. 2020, 21, 1347. https://doi.org/10.3390/ijms21041347

AMA Style

Lee H, Lee K, Lee S, Lee J, Jeong WT, Lim HB, Hyun TK, Yi S-J, Kim K. Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression. International Journal of Molecular Sciences. 2020; 21(4):1347. https://doi.org/10.3390/ijms21041347

Chicago/Turabian Style

Lee, Hyerim, Kyubin Lee, Sheunghun Lee, Jisu Lee, Won Tae Jeong, Heung Bin Lim, Tae Kyung Hyun, Sun-Ju Yi, and Kyunghwan Kim. 2020. "Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression" International Journal of Molecular Sciences 21, no. 4: 1347. https://doi.org/10.3390/ijms21041347

APA Style

Lee, H., Lee, K., Lee, S., Lee, J., Jeong, W. T., Lim, H. B., Hyun, T. K., Yi, S.-J., & Kim, K. (2020). Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression. International Journal of Molecular Sciences, 21(4), 1347. https://doi.org/10.3390/ijms21041347

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