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Published on: February 28, 2017
Wogonin inhibits osteoclast differentiation by inhibiting NFATc1 translocation into the nucleus
Xiaolin Geng1, Libin Yang1, Chao Zhang1
1Department of Orthopedic Surgery I, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Abstract:
The aim of the present study was to identify a natural product with the ability to inhibit nuclear factor of activated T cells c1 (NFATc1) translocation from the cytoplasm to the nucleus by high-throughput screening, and to investigate the effect of the natural product upon osteoclast differentiation and its underlying mechanism. An NFATc1 antagonist redistribution assay was performed in U2OS-NFATc1 cells against a natural product library, and Wogonin was found to have the ability to inhibit the NFATc1 translocation from the cytoplasm to the nucleus. The effect of Wogonin on NFATc1 transcription activation was further determined by luciferase assay. An osteoclast differentiation assay was executed to evaluate the effect of Wogonin on osteoclast differentiation. The effect of Wogonin upon the vital genes in osteoclast differentiation was investigated using fluorescent quantitative polymerase chain reaction analysis. The natural product Wogonin significantly inhibited the translocation of NFATc1 from the cytoplasm to the nucleus and its transcriptional activation activity. Wogonin also significantly inhibited osteoclast differentiation and decreased the transcription of osteoclast-associated immunoglobulin-like receptor, tartrate-resistant acid phosphatase and calcitonin receptor. In conclusion, the natural product Wogonin inhibited osteoclast differentiation through the inhibition of NFATc1 translocation from the cytoplasm to the nucleus, and thus the downregulation of genes associated with osteoclast differentiation, which marked Wogonin as a potential treatment for osteoporosis.
Insights
Wogonin, a natural product, inhibits nuclear factor of activated T cells c1 (NFATc1) translocation and osteoclast differentiation. This discovery offers potential new treatments for osteoporosis.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Osteoclast differentiation is crucial for bone remodeling and is implicated in bone diseases like osteoporosis.
- Nuclear factor of activated T cells c1 (NFATc1) plays a key role in osteoclast differentiation.
- Identifying natural products that modulate NFATc1 activity could lead to novel therapeutic strategies.
Purpose of the Study:
- To screen for natural products inhibiting NFATc1 translocation.
- To investigate the effects of identified compounds on osteoclast differentiation.
- To elucidate the molecular mechanisms underlying the observed effects.
Main Methods:
- High-throughput screening using an NFATc1 antagonist redistribution assay in U2OS-NFATc1 cells.
- Luciferase assay to assess NFATc1 transcriptional activity.
- Osteoclast differentiation assay and quantitative PCR to analyze gene expression.
Main Results:
- Wogonin was identified as a natural product that inhibits NFATc1 translocation and transcriptional activity.
- Wogonin significantly suppressed osteoclast differentiation.
- Wogonin decreased the expression of key osteoclast-related genes, including OSCAR, TRAP, and CALCR.
Conclusions:
- Wogonin inhibits osteoclast differentiation by blocking NFATc1 nuclear translocation and subsequent gene transcription.
- Wogonin demonstrates potential as a therapeutic agent for osteoporosis by targeting osteoclastogenesis.
- Further research into Wogonin's mechanism and efficacy is warranted for osteoporosis treatment.
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