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
