谷氨酰胺
软骨细胞
生物
谷氨酰胺酶
软骨发生
谷氨酰胺合成酶
谷氨酸脱氢酶
细胞生物学
生物化学
软骨
谷氨酸受体
解剖
间充质干细胞
氨基酸
受体
作者
Steve Stegen,Gianmarco Rinaldi,Shauni Loopmans,Ingrid Stockmans,Karen Moermans,Bernard Thienpont,Sarah-Maria Fendt,Peter Carmeliet,Geert Carmeliet
标识
DOI:10.1016/j.devcel.2020.05.001
摘要
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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