Excessive mechanical strain accelerates intervertebral disc degeneration by disrupting intrinsic circadian rhythm

• Published in: Experimental & molecular medicine Vol. 53; no. 12; pp. 1911 - 1923
• Main Authors: Ding, Sheng-Long, Zhang, Tai-Wei, Zhang, Qi-Chen, Ding, Wang, Li, Ze-Fang, Han, Guan-Jie, Bai, Jin-Song, Li, Xi-Lei, Dong, Jian, Wang, Hui-Ren, Jiang, Li-Bo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2021; Springer Nature B.V; 생화학분자생물학회
• Subjects: 13/1; 13/109; 13/89; 631/532/7; 631/80/128; 692/699/1670/407; Age Factors; Animal models; Animals; Biomarkers; Biomedical and Life Sciences; Biomedicine; BMAL1 protein; Cell Survival; Cellular Senescence; Chronic pain; Circadian Clocks - genetics; Circadian rhythm; Circadian Rhythm - genetics; Circadian rhythms; Degeneration; Degenerative disc disease; Disease Models, Animal; Disease Susceptibility; Extracellular matrix; Extracellular Matrix - metabolism; Intervertebral Disc Degeneration - diagnostic imaging; Intervertebral Disc Degeneration - etiology; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - pathology; Intervertebral discs; Low back pain; Magnetic Resonance Imaging; Male; Mechanical loading; Mechanical stimuli; Medical Biochemistry; Molecular Medicine; Nighttime; Posture; Radiography; Rats; Stem Cells; Stress, Mechanical; Tensile Strength; Therapeutic targets; Workers; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-021-00716-6

Night shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers. Lower back pain: Mechanical strain exacerbated by night shift work Working long shifts at times when the body should be at rest can have lasting effects on the intervertebral discs in the back, leading to chronic pain. Night shift workers are susceptible to developing certain health conditions because of chronic disruption to their circadian rhythms. Now, Li-Bo Jiang at Zhongshan Hospitial, Fudan University in Shanghai and co-workers across China have uncovered a link between circadian rhythm disruption and intervertebral disc degeneration. In experiments on human tissue samples and rat models, the team found that oscillation of the expression of clock-related genes and proteins was reduced in severely degenerated disc cells. Cellular clock mechanisms were disrupted in disc cells that had been repeatedly placed under mechanical strain at night. This disruption appears to influence degradation of the extracellular matrix, which the team believe may in turn accelerate disc degeneration.