Hydrogen peroxide pushed human cartilage cells towards an osteoarthritis-like state
This 2019 University of Auckland lab study exposed human cartilage cells to hydrogen peroxide, an inflammatory signal or calcium phosphate crystals. Each stress lowered SOX9, a master switch for making cartilage, raised the cartilage-cutting enzymes MMP13 and ADAMTS5, and disturbed the cells' internal clock.
What they did
Researchers at the University of Auckland took chondrocytes, the cells inside cartilage, from human cartilage that looked normal. They starved the cells of serum overnight, then fed them again with or without one of three stresses: hydrogen peroxide (an oxidant), IL-1 beta (an inflammatory signal) or basic calcium phosphate crystals.
They tracked two clock genes, PER2 and BMAL1, and markers of cartilage cell behaviour. They also turned PER2 down in normal and osteoarthritic cells, turned BMAL1 down further in osteoarthritic cells, and raised PER2 in a chondrocyte cell line called H5.
What they found
All three stresses lowered the peak level of BMAL1 and kept PER2 high for longer than in untreated cells. They also lowered SOX9 and raised MMP13 and ADAMTS5, two enzymes that break down cartilage.
Turning PER2 down partly blocked these effects. In osteoarthritic cells, lowering PER2 raised SOX9 and lowered ADAMTS5 and MMP13, while lowering BMAL1 further reduced SOX9 and raised MMP13. Raising PER2 in the H5 cell line raised ADAMTS5 and MMP13 and lowered SOX9.
What it can't tell us
These are cells in a dish, and each stress was given at one lab concentration. The abstract does not give the number of donors or how long the treatments lasted. The study did not measure glutathione, so it cannot say whether glutathione levels changed or whether more glutathione would have blunted the effect of hydrogen peroxide.
Why it matters
This study links oxidative stress directly to MMP13, one of the enzymes that break down cartilage. A single oxidant, hydrogen peroxide, was enough to move healthy human cartilage cells towards the pattern seen in osteoarthritis. Glutathione is one of the cell's own defences against oxidants (Forman 2009), which is why this paper sits in a glutathione library even though glutathione was not measured.
The paper
- 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.
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