This 2011 lab study stimulated cartilage cells from people with osteoarthritis or rheumatoid arthritis with IL-1 beta, which raised MMP13. Hyaluronan, the main lubricant in joint fluid, lowered that MMP13 and the signalling protein p-p38 in a dose-dependent way from 0.1 to 4 mg/ml. Blocking its receptor, CD44, reversed the effect.
Researchers took chondrocytes from patients with osteoarthritis or rheumatoid arthritis and stimulated them with interleukin-1 beta at 2 ng/ml. They measured MMP13 released into the culture medium and made inside cartilage, tested which MAP kinase pathway (p38, ERK or JNK) IL-1 beta used, added hyaluronan at 0.1, 1, 2 and 4 mg/ml, and blocked hyaluronan's main receptor, CD44, with an antibody.
IL-1 beta raised MMP13 secretion in both types of cells, and specific inhibitors showed it did so through p38. Hyaluronan lowered IL-1 beta-driven MMP13 and phosphorylated p38 in a dose-dependent way. At 4 mg/ml it cut p38 phosphorylation by more than 60%. Cells from rheumatoid arthritis showed more p-p38 than cells from osteoarthritis. Blocking CD44 significantly reversed hyaluronan's effect on both MMP13 and p-p38.
The hyaluronan went straight onto cells in a dish, at concentrations chosen for the lab. The abstract does not say how many patients donated cells. It does not tell us whether hyaluronan taken by mouth or injected reaches cartilage cells at these levels, or what it would do there.
Hyaluronan is best known as a lubricant. This study shows it also acting as a signal: through its receptor CD44 it turned down MMP13 in human cartilage cells, and more hyaluronan meant less MMP13. It also confirms p38 as one of the routes IL-1 beta uses to switch MMP13 on.
Yes, in lab studies. The inflammatory messenger IL-1 raised MMP13 in human cartilage and cartilage cells in several studies, and TNF-alpha did too. To switch the MMP13...
In human cartilage cells, MMP13 rose in response to inflammatory messengers such as IL-1, oxidative stress, calcium phosphate crystals, a disrupted cell body clock...