Cryptochromes at the Root of Arthritic Morning Stiffness

Atop a growing body of research that examines how rheumatoid arthritis (RA) symptoms are dictated by the body’s circadian rhythms, a recent study seems to explain why so many people-RA sufferers included-wake up each day with stiff joints.

RA is a disease that operates diurnally, expressing itself differently throughout the course of a 24-hour day as a result of various processes. The new paper, published in The FASEB Journal, points to a protein called cryptochrome as an important factor in widely-experienced morning stiffness.

Cryptochrome’s significant anti-inflammatory effects work by helping to regulate the body’s circadian cycle, activating those effects during the “dark” or sleep portion of the day in order to mitigate painful RA symptoms. Knocking the circadian clock out of sync can alter its ability to regulate inflammation.

The research team was able to demonstrate this by harvesting fibroblast-like synoviocyte (FLS) cells from healthy human and mice tissue. FLS cells maintain a 24-hour rhythm, but when cryptochrome was eliminated from the genotype, that rhythm was compromised and inflammatory reactions were increased.

Previous work by many of the same researchers has been able to determine the ways in which the body’s biological clock can impact inflammatory conditions. Increased release of melatonin, for example, can lead to an excess of collagen and development or exacerbation of arthritic symptoms. Glucocorticoids, which are anti-inflammatory agents, can be seen to circulate differently throughout the day in accordance with the circadian clock, reaching peak circulation not long after wakeup.

The new study, identifying the role of cyptochromes, combines with this previous data to give doctors and researchers new areas of treatment and study. Treatment could, perhaps, be more effective if timed to exploit the natural processes already occurring naturally in RA patients.

Thoru Pederson, Ph.D. and Editor-in-Chief of The FASEB Journal, says in a press release that this research "reminds us that inflammation, typically thought of as chronic and brittle, can, in fact, be nuanced--In this case, under the influence of the brain's suprachiasmatic nucleus, which controls the body's circadian physiology,” adding that "The clinical implications are far-reaching."