Passive cigarette smoking changes the circadian rhythm of clock genes in rat intervertebral discs

J Orthop Res. 2016 Jan;34(1):39-47. doi: 10.1002/jor.22941. Epub 2015 May 20.


We aimed to elucidate the molecular changes in intervertebral discs (IVDs) caused by passive smoking. Rats were subjected to 8 weeks of passive smoking; thereafter, their lumbar vertebrae were harvested. The annulus fibrosus and cartilage endplate (AF/CEP) were harvested together, and the nucleus pulposus (NP) was isolated separately. The expression of 27,342 rat genes was analyzed. In 3 "nonsmoking" rats, 96 of 112 genes whose expression varied ≥10-fold between the AF/CEP and NP were more highly expressed in the AF/CEP. With these differentially expressed genes, we uncovered novel AF/CEP and NP marker genes and indicated their possible novel functions. Although passive smoking induced less marked alteration in the gene expression profiles of both the AF/CEP and NP, multiple clock-related genes showed altered expression. These genes were expressed with a circadian rhythm in IVD cells, and most genes showed a phase shift of -6 to -9 h induced by passive smoking. Some clock-related genes showed abolished oscillation in the NP. Passive smoking also changed the expression levels of proteases and protease inhibitors and reduced the expression of NP marker genes. Thus, passive smoking induces changes in the circadian rhythm of a peripheral clock (IVD clock) that might be involved in molecular events related to IVD degeneration.

Keywords: cigarette smoking; circadian rhythm; intervertebral disc; microarray; phase shift.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm*
  • Gene Expression Profiling
  • Intervertebral Disc / metabolism*
  • Male
  • Rats, Sprague-Dawley
  • Tobacco Smoke Pollution / adverse effects*


  • Tobacco Smoke Pollution