論文 - 詳細
| RRC ID | 85970 |
|---|---|
| 著者 | Koga A, Nagai-Yoshioka Y, Yamasaki R, Adachi Y, Fujii W, Ariyoshi W. |
| タイトル | Molecular Mechanisms of Curdlan-Induced Suppression of NFATc1 Expression in Osteoclasts. |
| ジャーナル | J Cell Biochem |
| Abstract |
Osteoclasts derived from hematopoietic stem cells express immunoreceptors on their cell surface. Previously, we showed that the β-glucan curdlan suppressed osteoclastogenesis via binding to dectin-1, a pattern recognition receptor. Curdlan negatively regulates osteoclast differentiation and bone resorption capacity by suppressing the expression of nuclear factor of activated T cells 1 (NFATc1), a master factor for osteoclast differentiation, in a dectin-1-dependent manner; however, the mechanism involved in this process has not yet been fully elucidated. In this study, we aimed to elucidate the molecular mechanism involved in the suppression of RANKL-induced osteoclast differentiation by curdlan. Real-time RT-qPCR results showed that curdlan suppressed the expression of NFATc1 in cells of the osteoclast progenitor cell line RAW264.7 overexpressing dectin-1 (d-RAW cells), without altering the expression of negative regulators. Therefore, we examined the effect of curdlan on the NF-κB pathway, which is important for the induction of NFATc1 expression. Western blot analysis results showed that curdlan addition suppressed RANKL-induced NF-κB activation in the vector control line (c-RAW) cells with low expression of dectin-1, in d-RAW cells, and the parental RAW264.7 (RAW) cells. The results of tartrate-resistant alkaline phosphatase staining and real-time RT-qPCR showed that curdlan addition suppressed osteoclast differentiation in RAW cells, suggesting the presence of a dectin-1-independent modification system. Finally, we focused on the complement receptor 3 (CR3), which binds β-glucan, and revealed that blocking the binding of β-glucan to the CD11b molecule, a component of CR3, by neutralizing antibody, recovered the suppression of IκBα degradation by curdlan. These results suggest that the suppression of osteoclast differentiation by curdlan involves not only the dectin-1-dependent pathway but also the negative regulation of NFATc1 via modification of the NF-κB pathway via CR3 recognition. The results of this study may aid to establish treatment methods for metabolic bone diseases and inflammatory bone destruction and to clarify their pathogenesis. |
| 巻・号 | 126(1) |
| ページ | e30682 |
| 公開日 | 2025-1-1 |
| DOI | 10.1002/jcb.30682 |
| PMID | 39606840 |
| MeSH | Animals Cell Differentiation / drug effects Gene Expression Regulation* / drug effects Lectins, C-Type / genetics Lectins, C-Type / metabolism Mice NF-kappa B / metabolism NFATC Transcription Factors* / genetics NFATC Transcription Factors* / metabolism Osteoclasts* / cytology Osteoclasts* / drug effects Osteoclasts* / metabolism RANK Ligand / metabolism RANK Ligand / pharmacology RAW 264.7 Cells Signal Transduction / drug effects beta-Glucans* / pharmacology |
| IF | 4.237 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |