PUBLICATION

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

Authors
Lee, H., Lee, K., Lee, S., Lee, J., Jeong, W.T., Lim, H.B., Hyun, T.K., Yi, S.J., Kim, K.
ID
ZDB-PUB-200225-1
Date
2020
Source
International Journal of Molecular Sciences   21(4): (Journal)
Registered Authors
Keywords
Lentinula edodes, NFATc1, osteoclast, osteoporosis
MeSH Terms
  • Acetates/chemistry*
  • Animals
  • Bone Resorption/metabolism
  • Bone and Bones/metabolism
  • Cell Differentiation/drug effects
  • Cell Survival/drug effects
  • Disease Models, Animal
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Expression Regulation/drug effects
  • HEK293 Cells
  • Humans
  • NF-kappa B/metabolism
  • NFATC Transcription Factors/genetics
  • NFATC Transcription Factors/metabolism*
  • Neoplasm Proteins/metabolism
  • Osteoblasts/metabolism
  • Osteoclasts/metabolism
  • Osteogenesis/drug effects*
  • Osteogenesis/genetics
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand/drug effects*
  • RANK Ligand/genetics
  • RANK Ligand/metabolism
  • Shiitake Mushrooms/chemistry*
  • Signal Transduction/drug effects*
  • Transcription Factors/metabolism
  • Transcriptome
  • Zebrafish
PubMed
32079267 Full text @ Int. J. Mol. Sci.
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.
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