Inflammation, oxidative stress and calcium crystals upset the cartilage cell clock and raise MMP13

What they did

Researchers took chondrocytes from cartilage that looked normal, starved them of serum overnight, then fed them again with or without one of three stresses: IL-1 beta at 10 ng/mL, hydrogen peroxide at 100 µM or basic calcium phosphate crystals at 50 µg/mL. They tracked clock genes and cartilage markers. They then knocked down PER2 or BMAL1 in normal and osteoarthritic cells, and over-expressed PER2 in the H5 chondrocyte cell line.

What they found

All three stresses lowered the peak of BMAL1 and kept PER2 high for longer. They also lowered SOX9, a master switch for making cartilage, and raised ADAMTS5 and MMP13. Knocking down PER2 partly blocked each stress's effect. In osteoarthritic chondrocytes, PER2 knockdown raised SOX9 and lowered ADAMTS5 and MMP13, at RNA and protein level, while cutting BMAL1 further lowered SOX9 and raised MMP13. Over-expressing PER2 in the 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 applied at one fixed lab concentration. The abstract does not give the number of donors. Gene knockdown and over-expression are research tools, not things that happen in a joint, so the study shows the clock can steer MMP13 in cells, not that clock changes drive cartilage loss in people.

Why it matters

It links three separate triggers, inflammation, oxidative stress and crystals, through one route: the cartilage cell's clock. Each pushed MMP13 up, and moving the clock genes moved MMP13 up or down. It also shows MMP13 and ADAMTS5 rising together under the same stresses.

The paper

1. 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.
   PMID 30403881DOI 10.1080/07420528.2018.1540493

Read next