Review: with age, cartilage cells make more oxidants than their defences can handle
This 2019 review sets out the evidence that ageing cartilage cells produce more reactive oxygen species than their antioxidant defences can cope with. The authors argue that the main harm is disrupted cell signalling, not only direct damage, and that this contributes to cartilage breakdown and cell death in osteoarthritis.
What they did
This is a review of published research, not a new experiment. The authors summarised what is known about reactive oxygen species (ROS), the oxygen-based molecules that can damage cells, in chondrocytes, the cells inside cartilage, and how ageing changes the balance between ROS production and antioxidant capacity.
What they found
The review names the ROS chondrocytes make that have drawn the most attention: superoxide, hydrogen peroxide, nitric oxide and peroxynitrite. In excess they cause oxidative damage but, the authors suggest, more importantly they disrupt signalling pathways that respond to the cell's oxidation state, including Akt and MAP kinase signalling.
Age-related changes in mitochondria, the cell's power units, and lower activity of the mitochondrial antioxidant enzyme SOD2 are linked to the rise in chondrocyte ROS with age. Peroxiredoxins, enzymes that remove hydrogen peroxide, can be switched off by over-oxidation, and this over-oxidation is more common with age and in osteoarthritic cartilage.
In mice, removing SOD2 or Nrf2, a master regulator of antioxidant genes, led to more severe osteoarthritis, while boosting these defences or giving antioxidants aimed at the mitochondria reduced it.
What it can't tell us
A review adds no new data, and its picture depends on the studies the authors chose. The protective effects it describes come from mice. The abstract does not discuss glutathione directly, and it does not show that any antioxidant treatment slows osteoarthritis in people. Its conclusion that targeting specific antioxidant systems may help is a suggestion for future work.
Why it matters
This review is a good map of why oxidative stress matters in ageing cartilage. Its main point is that too many oxidants scramble the signals a cartilage cell uses to decide whether to repair, survive or die. That framing helps explain why later studies look at antioxidant systems, glutathione among them, rather than oxidant damage alone.
The paper
- Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med 2019.
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