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Ethyl acetate fraction of Lentinula edodes (LEA) inhibits osteoclastogenesis by suppressing NFATc1 expression

ABSTRACT: To screen for altered gene expression during osteoclastogenesis, BMM cells treated with RANKL or RANKL+LEA were subjected to gene expression profiling.

ORGANISM(S): Mus musculus

PROVIDER: GSE142866 | GEO | 2020/02/24

REPOSITORIES: GEO

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

Project description: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-?B) signaling pathways in response to receptor activation of NF-?B 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.

| S-EPMC7072883 | biostudies-literature

Ethyl acetate fraction of Lentinula edodes (LEA) inhibits osteoclastogenesis by suppressing NFATc1 expression

Project description:Ethyl acetate fraction of Lentinula edodes (LEA) inhibits osteoclastogenesis by suppressing NFATc1 expression

| PRJNA598711 | ENA

Abeliophyllum distichum Nakai Extract exerts anti-osteoporotic effects by suppressing RANKL-induced osteoclastogenesis

Project description:To screen for altered gene expression during osteoclastogenesis, BMM cells treated with RANKL or RANKL+LE were subjected to gene expression profiling.

2020-09-23 | GSE152479 | GEO

TMBIM6 deficiency leads to bone loss by accelerating osteoclastogenesis

Project description:To screen for altered gene expression during osteoclastogenesis, BMM cells depleted of TMBIM6 with or without RANKL were subjected to gene expression profiling.

2023-07-10 | GSE231889 | GEO

Chromatin accessibility-based epigenetic landscape in osteoclastogenesis [RNA-seq]

Project description:In this study, we showed chromatin accessibility-based epigenetic landscape in osteoclastogenesis. To reveal the affected genes by alteration in histone acetylation states after RANKL stimulation, we supplemented sodium acetate, which increased histone acetylation, to OC precursors. Then we conducted RNA-seq with BMM (D0), OC precursors (D1), and OC precursors treaed with sodium acetate (ACD1).

2023-01-01 | GSE212722 | GEO

Macrosynteny analysis between Lentinula edodes and Lentinula novae-zelandiae reveals signals of domestication in Lentinula edodes.

Project description:The basidiomycete fungus Lentinula novae-zelandiae is endemic to New Zealand and is a sister taxon to Lentinula edodes, the second most cultivated mushroom in the world. To explore the biology of this organism, a high-quality chromosome level reference genome of L. novae-zelandiae was produced. Macrosyntenic comparisons between the genome assembly of L. novae-zelandiae, L. edodes and a set of three genome assemblies of diverse species from the Agaricomycota reveal a high degree of macrosyntenic restructuring within L. edodes consistent with signal of domestication. These results show L. edodes has undergone significant genomic change during the course of its evolutionary history, likely a result of its cultivation and domestication over the last 1000 years.

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NOTCH2 Promotes Osteoclast Maturation and Metabolism and Modulates the Transcriptome Profile During Osteoclastogenesis

Project description:Bone marrow derived macrophages (BMM) from Notch2tm1.1Ecan, harboring a NOTCH2 gain-of-function mutation, and control mice were cultured with macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). Bulk RNA-Seq revealed enhanced cell metabolism, aerobic respiration, and mitochondrial function, all associated with osteoclastogenesis, in Notch2tm1.1Ecan cells. Single cell RNA-Seq data of BMMs treated with M-CSF or M-CSF and RANKL for 3 days identified 11 well-defined cellular clusters. There was an increased number of cells expressing gene markers associated with the osteoclast and with related clusters in Notch2tm1.1Ecan than in control BMMs.

2024-01-03 | GSE248138 | GEO

NOTCH2 Promotes Osteoclast Maturation and Metabolism and Modulates the Transcriptome Profile During Osteoclastogenesis

2024-01-03 | GSE248137 | GEO

A novel small molecule derived from Lentinula edodes targets PRDX1 to inhibit RANKL-induced osteoclast differentiation and rescues the osteoporotic phenotype [Denatonium]

Project description:Bone remodeling, crucial for skeletal integrity, involves osteoclasts and osteoblasts. Osteoclastogenesis, regulated by NFATc1, is activated by c-Fos and NF-κB signaling in response to RANKL. Excessive RANKL signaling contributes to bone loss pathology. Here we reveal denatonium as an inhibitor of RANKL-induced osteoclast differentiation through the p65 pathway. RNA-seq identified downregulated osteoclast-related genes. Affinity chromatography pinpointed 35 denatonium-interacting proteins, with PRDX1 showing specificity. PRDX1 deficiency led to osteoporosis with increased osteoclast activity and enhanced RANKL-induced osteoclast formation. Denatonium blocked PRDX1 lysosomal degradation, stabilizing PRDX1. Through transcription factor binding site analysis, p65 emerged as a major target suppressed by the denatonium-PRDX1 interaction. Chromatin immunoprecipitation confirmed that the denatonium-PRDX1 complex inhibited p65 enrichment at promoter regions critical for osteoclast differentiation. In an osteoporosis animal model, denatonium treatment restored bone health. This study uncovers denatonium's novel role in bone formation regulation by selectively targeting PRDX1, suggesting its potential in osteoporosis treatment.

2024-06-30 | GSE248992 | GEO

Development stages of Lentinula edodes

Project description:Gene expression profiles at different development stages and different growth medium of Lentinula edodes (L54) are comparied. Keywords: time-course

2005-01-20 | GSE2167 | GEO

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