Public health

Intervertebral discs have circadian clocks

Wednesday, 10 Aug 2016

Disturbed circadian rhythms during normal ageing or in shift workers may contribute to degeneration of intervertebral discs and low back pain, new research suggests.

A team from Manchester, UK, identified clear circadian rhythms in mouse disc material and human disc cells.

They found a total of 607 genes with 24-hour cycles of expression, representing several essential pathways of disc physiology.

These beneficial natural cycles could be blocked by treatment with interleukin-1β, but not by tumour necrosis factor α.

“Anti-inflammatory drugs that selectively target IL-1 are more likely to bring therapeutic benefit,” they concluded.

“Circadian rhythms coordinate tissue-specific physiology with light/darkness, rest/activity, feeding cycles and body temperature fluctuations,” they said.

“Existing evidence suggests that the IVD is a highly rhythmic tissue, experiencing a diurnal cycle of higher loading (activity phase) followed by a period of low-load recovery (resting phase).”

Shift work, which disrupts circadian rhythms, has been associated with higher risks of low back pain and IVD degeneration.

This new research established for the first time that IVDs contain autonomous circadian clocks which respond to age and cytokines, and control key pathways involved in the homeostasis of IVDs.

Circadian patterns were identified in genes and pathways implicated in IVD physiology and pathology, including those involved in matrix homeostasis and repair, mitochondrial function and fatty acid metabolism.

The adverse effect of pro-inflammatory cytokines on these natural rhythms was also a new discovery.

“Therefore, there is the possibility of stabilising IVD clock rhythm as a novel strategy to combat tissue catabolism,” they said.

They noted that IVD degeneration is among the most prevalent musculoskeletal disorders, affecting one in five people under 60 and more than half of people older than 60. Low back pain, often associated with IVD degeneration, is the leading cause of years lived with disability in developed countries.

The study was reported in the Annals of the Rheumatic Diseases.

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