What does oxidative stress do to cartilage?
Oxidative stress is when a cell makes more reactive oxygen species than its antioxidants can clear. In cartilage it disrupts the cells' signalling and contributes to cartilage breakdown and cell death (Bolduc 2019). In cells from healthy human cartilage, hydrogen peroxide lowered SOX9, the cells' identity switch, and raised MMP13, the enzyme that cuts cartilage collagen (Rong 2019).
More than wear on the surface
Cartilage cells produce reactive oxygen species as part of normal life, including superoxide, hydrogen peroxide and nitric oxide. A 2019 review sets out evidence that with age their production outpaces the cells' antioxidant capacity, and that the bigger problem is not just direct damage but the disruption of redox-regulated signalling such as Akt and MAP kinase (Bolduc 2019).
It changes what the cell does
In a University of Auckland study of cells from macroscopically normal human cartilage, hydrogen peroxide, an inflammatory signal (IL-1β) and calcium crystals each lowered SOX9 and raised the cartilage-cutting enzymes MMP13 and ADAMTS5 (Rong 2019). In older human chondrocytes, oxidative damage to peroxiredoxins tipped the cells toward a death signal (Collins 2016).
It can kill the cell outright
Cartilage cells drained of glutathione died more readily under oxidant stress (Del Carlo 2003). A newer line of research looks at ferroptosis, an iron-dependent form of cell death that GPX4, a glutathione-dependent enzyme, normally prevents. GPX4 was lower in damaged cartilage from 55 osteoarthritis patients than in undamaged cartilage, and lowering it worsened osteoarthritis in an animal model (Miao 2022).
What the cell defends with
Glutathione is the cell's own front-line antioxidant (Forman 2009). In rats, NAC, which supplies cysteine for glutathione, held back MMP13 and type II collagen loss when given by mouth (Kaneko 2019).
Other questions people ask
Is oxidative stress the same as inflammation?
No, but they feed each other. In human cartilage cells an inflammatory signal and hydrogen peroxide had similar effects on SOX9 and MMP13 (Rong 2019).
Does exercise cause oxidative stress in cartilage?
Loading does use up cartilage glutathione in the short term. In cow cartilage, compressive loading oxidised glutathione and unloaded periods were needed for it to recover (Zhu 2020).
Sources
- Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med 2019.
- Rong J, Zhu M, Munro J et al. Altered expression of the core circadian clock component PERIOD2 contributes to osteoarthritis-like changes in chondrocyte activity. Chronobiol Int 2019.
- Collins JA, Wood ST, Nelson KJ et al. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes. J Biol Chem 2016.
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
- Miao Y, Chen Y, Xue F et al. Contribution of ferroptosis and GPX4's dual functions to osteoarthritis progression. EBioMedicine 2022.
- Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009.
- Kaneko Y, Tanigawa N, Sato Y et al. Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model. Sci Rep 2019.
- 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.
Read next
How are cartilage glutathione and MMP13 connected?
Oxidative stress is one of the signals that switches on MMP13, the enzyme that cuts cartilage collagen. In cells from healthy human cartilage, hydrogen peroxide raised...
What is ferroptosis, and what does it have to do with cartilage glutathione?
Ferroptosis is an iron-dependent form of cell death driven by damage to cell membranes. GPX4, an enzyme that needs glutathione to work, is the cell's main brake on it....
Does loading a joint use up cartilage glutathione?
In the short term, yes. In cow cartilage, cyclic compressive loading oxidised glutathione, and unloaded periods were needed for it to recover and for the tissue's total...
What happens to cartilage glutathione with age?
With age, cartilage cells tend to hold more of their glutathione in its used, oxidised form and cope worse with oxidative stress. In human cartilage cells, more than...