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
-
- Transcriptome
- NFATC Transcription Factors/genetics
- NFATC Transcription Factors/metabolism*
- Osteoblasts/metabolism
- Bone Resorption/metabolism
- Proto-Oncogene Proteins c-fos
- HEK293 Cells
- Animals
- Cell Survival/drug effects
- Disease Models, Animal
- Zebrafish
- RANK Ligand/drug effects*
- RANK Ligand/genetics
- RANK Ligand/metabolism
- Bone and Bones/metabolism
- Humans
- Transcription Factors/metabolism
- Osteoclasts/metabolism
- NF-kappa B/metabolism
- Cell Differentiation/drug effects
- Gene Expression Regulation/drug effects
- Down-Regulation
- Neoplasm Proteins/metabolism
- Signal Transduction/drug effects*
- Osteogenesis/drug effects*
- Osteogenesis/genetics
- Shiitake Mushrooms/chemistry*
- Acetates/chemistry*
- Gene Expression Profiling
- PubMed
- 32079267 Full text @ Int. J. Mol. Sci.
Citation
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):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping