論文 - 詳細
| RRC ID | 58785 |
|---|---|
| 著者 | van Gastel N, Stegen S, Eelen G, Schoors S, Carlier A, Daniëls VW, Baryawno N, Przybylski D, Depypere M, Stiers PJ, Lambrechts D, Van Looveren R, Torrekens S, Sharda A, Agostinis P, Lambrechts D, Maes F, Swinnen JV, Geris L, Van Oosterwyck H, Thienpont B, Carmeliet P, Scadden DT, Carmeliet G. |
| タイトル | Lipid availability determines fate of skeletal progenitor cells via SOX9. |
| ジャーナル | Nature |
| Abstract |
The avascular nature of cartilage makes it a unique tissue1-4, but whether and how the absence of nutrient supply regulates chondrogenesis remain unknown. Here we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids. When lipids are scarce, skeletal progenitors activate forkhead box O (FOXO) transcription factors, which bind to the Sox9 promoter and increase its expression. Besides initiating chondrogenesis, SOX9 acts as a regulator of cellular metabolism by suppressing oxidation of fatty acids, and thus adapts the cells to an avascular life. Our results define lipid scarcity as an important determinant of chondrogenic commitment, reveal a role for FOXO transcription factors during lipid starvation, and identify SOX9 as a critical metabolic mediator. These data highlight the importance of the nutritional microenvironment in the specification of skeletal cell fate. |
| 巻・号 | 579(7797) |
| ページ | 111-117 |
| 公開日 | 2020-3-1 |
| DOI | 10.1038/s41586-020-2050-1 |
| PII | 10.1038/s41586-020-2050-1 |
| PMID | 32103177 |
| PMC | PMC7060079 |
| MeSH | Animals Bone and Bones / blood supply Bone and Bones / cytology* Cellular Microenvironment* Chondrocytes / cytology Chondrocytes / metabolism Chondrogenesis* Fatty Acids / metabolism Female Food Deprivation Forkhead Transcription Factors / metabolism Lipid Metabolism* Male Mice Mice, Inbred C57BL Osteogenesis Oxidation-Reduction SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism* Signal Transduction Stem Cells / cytology* Stem Cells / metabolism* Wound Healing |
| IF | 42.779 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 159 |
| 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 | 10T1/2(RCB0247) |