期刊
DEVELOPMENTAL CELL
卷 53, 期 5, 页码 530-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2020.05.001
关键词
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资金
- Research Foundation - Flanders [FWO: G.0964.14, G.0A42.16, G.0B3418]
- KU Leuven [C24/17/077]
- long-term structural funding - Methusalem Funding by the Flemish Government
- KU Leuven Methusalem
- Emmanuel van der Schueren - Kom op tegen Kanker foundation
- FWO [1137117N, 1137119N]
Correct functioning of chondrocytes is crucial for long bone growth and fracture repair. These cells are highly anabolic but survive and function in an avascular environment, implying specific metabolic requirements that are, however, poorly characterized. Here, we show that chondrocyte identity and function are closely linked with glutamine metabolism in a feedforward process. The master chondrogenic transcription factor SOX9 stimulates glutamine metabolism by increasing glutamine consumption and levels of glutaminase 1 (GLS1), a rate-controlling enzyme in this pathway. Consecutively, GLS1 action is critical for chondrocyte properties and function via a tripartite mechanism. First, glutamine controls chondrogenic gene expression epigenetically through glutamate dehydrogenase-dependent acetyl-CoA synthesis, necessary for histone acetylation. Second, transaminase-mediated aspartate synthesis supports chondrocyte proliferation and matrix synthesis. Third, glutamine-derived glutathione synthesis avoids harmful reactive oxygen species accumulation and allows chondrocyte survival in the avascular growth plate. Collectively, our study identifies glutamine as a metabolic regulator of cartilage fitness during bone development.
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