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

International Journal of Molecular Sciences

TaeKyung Hyun¹  HeungBin Lim¹  WonTae Jeong¹  Kyunghwan Kim²  Sheunghun Lee²  Hyerim Lee²  Kyubin Lee²  Sun-Ju Yi²  Jisu Lee² 

[1] Department of Industrial Plant Science and Technology, Chungbuk National University, Cheongju 28644, Korea;School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea;

关键词: lentinula edodes;    osteoclast;    nfatc1;    osteoporosis;   

DOI  :  10.3390/ijms21041347

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown