Concept: People have been suffering from morning stiffness for ages. The common feeling is that we sleep absence of pain, but when we wake up things just starting going bad to worse. Though many theories were placed to explain the phenomena of morning stiffness but none is able to explain the observation completely.
In a new research it is proved that biological clock of human body regulated inflammation especially during night sleep. With the help of a protein named Cryptochrome, the body actively represses inflammatory pathways within the affected limbs during the night.
Observations: Researchers from the field of inflammatory diseases have common observations such as:
a: There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis.
b: Disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases.
Methodology: In order to investigate the mechanistic links between the biological clock and pathways underlying inflammatory arthritis, an animal model was developed where mice were administered collagen (or saline as a control) to induce arthritis. Furthermore, exposure of mice to constant light was carried to disrupt the clock in peripheral tissues, to record any loss of the nighttime repression of local inflammation.
The salient observations of the study were:
a: The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression.
b: Inflammatory markers were significantly repressed during the dark phase.
c: Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation.
Researchers attributed these findings to the ability of protein, called Cryptochrome, which have proven anti-inflammatory effects. Formed by the body's "biological clock" Cryptochrome actively represses inflammatory pathways within the affected limbs during the night.
To double check their findings, the researchers harvested cells from joint tissue of healthy mice called fibroblast-like synoviocytes (FLSs) which 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 highlighted that importance of cryptochrome gene product of cryptochrome protein. To test this hypothesis, researchers administered drugs designed to activate the protein to determine if protection against inflammation could be achieved-and it was.
The authors conclude as “that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.”
Article citation: Gibbs, J. E.; et. al. The circadian clock regulates inflammatory arthritis. 2016, doi:10.1096/fj.201600353R