論文 - 詳細
| RRC ID | 74469 |
|---|---|
| 著者 | Tanaka T, Takahashi A, Kobayashi Y, Saito M, Xiaolong S, Jingquan C, Ito Y, Kato T, Ochi H, Sato S, Yoshii T, Okawa A, Carlsson P, Inose H. |
| タイトル | Foxf2 represses bone formation via Wnt2b/β-catenin signaling. |
| ジャーナル | Exp Mol Med |
| Abstract |
Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture. |
| 巻・号 | 54(6) |
| ページ | 753-764 |
| 公開日 | 2022-6-1 |
| DOI | 10.1038/s12276-022-00779-z |
| PII | 10.1038/s12276-022-00779-z |
| PMID | 35668101 |
| PMC | PMC9256714 |
| MeSH | Animals Cell Differentiation / genetics Female Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Glycoproteins / metabolism Mice Mice, Knockout Osteoblasts / metabolism Osteogenesis / genetics Osteoporosis* / genetics Wnt Proteins / metabolism Wnt Signaling Pathway* beta Catenin / genetics beta Catenin / metabolism |
| IF | 5.418 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | ST2 (RCB0224) |