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Growing cartilage cells use glutamine to make glutathione and survive without blood vessels

GlutamineAnimalLab2020

This 2020 laboratory and animal study found that the identity and function of cartilage cells in the growing skeleton are closely tied to how they use glutamine, an amino acid. SOX9, the master switch for cartilage cells, raised glutamine use, and glutathione made from glutamine kept oxidants in check so the cells could survive without a blood supply.

Evidence typeAnimal and Lab
Who or what was studiedGrowth-plate chondrocytes during bone development (species and numbers not given in the abstract)
Dose and durationNot stated in the abstract

What they did

The researchers studied chondrocytes, the cells inside cartilage, in the growth plate, the cartilage near the ends of growing bones that is responsible for bone growth. They examined how SOX9, the main gene switch that makes a cell a cartilage cell, affects glutamine use, and what happens when the enzyme GLS1, which controls the first step of glutamine use, is not working.

What they found

SOX9 increased glutamine use by raising glutamine consumption and the level of GLS1. GLS1 was critical to cartilage cell function in three ways.

First, glutamine helped switch on cartilage genes by supplying the material for chemical tags on DNA-packaging proteins. Second, it supplied aspartate, which supported cell growth and matrix production. Third, glutamine was used to make glutathione, which stopped harmful reactive oxygen species building up and allowed the cells to survive in the growth plate, which has no blood vessels.

What it can't tell us

The study concerns growth-plate cartilage during bone development, not the joint cartilage of adults or older people. The abstract does not name the species or the methods in detail. It does not test whether eating more glutamine changes glutathione in cartilage.

Why it matters

This is a clear demonstration that cartilage cells make their own glutathione from raw materials they take in, and that this matters for their survival in a tissue with no blood supply. It also places glutamine, as well as glycine and cysteine, in the supply chain for cartilage glutathione.

The paper

  1. Stegen S, Rinaldi G, Loopmans S et al. Glutamine Metabolism Controls Chondrocyte Identity and Function. Dev Cell 2020.
Last reviewed Every study cited here is indexed on PubMed. How we read the evidence