A protein created by the body’s “biological clock” (circadian) that actively represses inflammatory pathways during the night is responsible for that stiffness many feel in the morning, says new research published online in The FASEB Journal.
Called CRYPTOCHROME, the protein has proven anti-inflammatory properties in cultured cells, which present potential new opportunities for the development of drugs that may be used to treat inflammatory and autoimmune diseases like rheumatoid arthritis.
“By understanding how the biological clock regulates inflammation, we can begin to develop new treatments, which might exploit this knowledge,” said Julie Gibbs, Ph.D., a researcher involved in the work and arthritis research UK career development fellow at the Centre for Endocrinology and Diabetes at the Institute of Human Development at the University of Manchester, United Kingdom. “Furthermore, by adapting the time of day at which current drug therapies are administered, we may be able to make them more effective.”
Gibbs and colleagues made the discovery by harvesting cells from joint tissue of healthy mice as well as humans. These cells, called “fibroblast-like synoviocytes,” are important in the pathology that underlies inflammatory arthritis. Each of these cells keeps a 24-hour rhythm, and when this rhythm was disrupted by knocking out the cryptochrome gene there was an increased inflammatory response.
This suggests that the cryptochrome gene product, the CRYPTOCHROME protein, has significant anti-inflammatory effects. To test this hypothesis, the UK researchers administered drugs designed to activate the protein to determine if protection against inflammation could be achieved. The result? It was.
“This study 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,” said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. “The clinical implications are far-reaching.”