Cartilage holds more glutathione than nearby joint tissues, and loading oxidises it
This 2020 paper combines a review with new experiments in rat, cow and mouse tissue. Cartilage had more glutathione than the meniscus or the knee's fat pad but was more prone to age-related glutathione oxidation. Under repeated compression its glutathione oxidised and needed unloaded rest periods to recover.
What they did
The authors reviewed the ideas of resistance (how well cartilage cells withstand a stress) and resilience (how quickly they recover) using glutathione as the example. They then tested these ideas in three animal models.
First, they compared glutathione in joint tissues from rats aged 10 and 30 months, and cultured rat kneecaps with an inflammatory signal, IL-1 beta, to look at protection by N-acetylcysteine (NAC). Second, they put cow cartilage through cyclic compression of different lengths and patterns. Third, they challenged cartilage cells from normal mice and from mice lacking a gene called Sirt3 with menadione, a chemical that generates oxidants, and tracked the ratio of reduced to oxidised glutathione (GSH:GSSG) over time.
What they found
Glutathione was more plentiful in cartilage than in the meniscus or the fat pad below the kneecap, but cartilage glutathione was also more likely to become oxidised with age.
The effect of compression depended on how long it lasted. Glutathione oxidised under load and needed unloaded periods to recover and to raise total antioxidant capacity. An oxidant challenge made cells more resistant by raising glutathione and the GSH:GSSG ratio, especially in cells lacking Sirt3, but those cells recovered more slowly. The abstract does not report the NAC result from the rat kneecap experiment.
What it can't tell us
All of the new data come from animals: rats, cow cartilage and mouse cells. Rats and cows are not people, and loading cow cartilage in a machine is not the same as walking on a human knee. The abstract does not give sample sizes, the loading settings or the menadione dose.
It shows that loading and age change cartilage glutathione in these models. It does not show what happens in older human joints, or whether supplying anything from outside changes the pattern.
Why it matters
This is the clearest source for two ideas: cartilage is rich in glutathione compared with the tissues around it, and mechanical loading uses that glutathione up for a while. The finding that cartilage needs rest periods to restore its glutathione gives a picture of glutathione as a reserve that is spent and refilled, rather than a fixed amount.
The paper
- Zhu S, Makosa D, Miller B et al. Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis. Connect Tissue Res 2020.
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