Mechanical Stretch Induces Annulus Fibrosus Cell Senescence through Activation of the RhoA/ROCK Pathway

• Published in: BioMed research international 2021, Vol.2021 (1), p.5321121-5321121
• Main Authors: Ning, Li, Gao, Lei, Zhang, Fan, Li, Xiaoxiao, Wang, Tingting
• Format: Article
• Language: English
• Subjects: Aging; Animals; Annuli; Annulus Fibrosus - cytology; Annulus Fibrosus - drug effects; Annulus Fibrosus - physiology; Back pain; Biology; Cell activation; Cell culture; Cell cycle; Cell growth; Cell Proliferation; Cells; Cells, Cultured; Cellular Senescence - physiology; Cellular signal transduction; Compression; Degenerative disc disease; Elongation; G1 Phase Cell Cycle Checkpoints; Gene expression; Guanosine triphosphatase; Intervertebral Disc Degeneration - etiology; Intervertebral Disc Degeneration - pathology; Intervertebral Disc Degeneration - physiopathology; Intervertebral discs; Intervertebral disk; Kinases; Mechanical properties; mRNA; Nucleus pulposus; p53 Protein; Physiological aspects; Physiological research; Protein kinase; Protein Kinase Inhibitors - pharmacology; Proteins; Rats; Rats, Sprague-Dawley; rho GTP-Binding Proteins - metabolism; Rho-associated kinase; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; RhoA protein; Rocks; Senescence; Signal transduction; Signal Transduction - drug effects; Stress, Mechanical; Telomerase; Telomerase - metabolism; Thiazoles - pharmacology; Urea - analogs & derivatives; Urea - pharmacology; Variance analysis
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2021/5321121

Background. Intervertebral disc is responsible for absorbing and transmitting mechanical compression. Under physiological conditions, the peripheral annulus fibrosus (AF) cells are subjected to different magnitudes of transverse mechanical stretch depending on the swelling of the central nucleus pulposus tissue. However, the biological behavior of AF cells under mechanical stretch is not well studied. Objective. This study was performed to study the effects of mechanical tension on AF cell senescence and the potential signaling transduction pathway. Methods. Rat AF cells were made to experience different magnitudes of mechanical stretch (2% elongation and 20% elongation for 4 hours every day at 1 Hz) in a 10-day experiment period. The inhibitor RKI-1447 of the Rho-associated coiled-coil–containing protein kinases (ROCK) was added along with culture medium to investigate its role. Cell proliferation, cell cycle, telomerase activity, and expression of senescence markers (p16 and p53) were analyzed. Results. We found that 20% elongation significantly decreased cell proliferation, promoted G0/G1 cell cycle arrest, decreased telomerase activity, and upregulated mRNA/protein expression of p16 and p53. Moreover, the inhibitor RKI-1447 partly resisted effects of 20% elongation on these parameters of cell senescence. Conclusion. High mechanical stretch obviously induces AF cell senescence through the RhoA/ROCK pathway. This study provides us a deeper understanding on the AF cell’s behavior under mechanical stretch.