Abstract
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.
Highlights
Intervertebral disc degeneration is a main cause of low back pain which often results in disability and productivity limitation around the world [1]
Activation of RhoA/Rho-associated coiled-coil–containing protein kinases (ROCK) signaling participates in regulating cell proliferation and proliferation [21]. When we inhibited this pathway by the specific inhibitor RKI-1447 in the 20% elongation group, we found that RKI-1447 partly reversed cell proliferation potency, attenuated G0/G1 cell cycle arrest, increased telomerase activity, and downregulated mRNA/ protein expression of senescence molecules (p16 and p53)
We observed the effects of mechanical stretch on annulus fibrosus (AF) cell senescence and investigated the role of the RhoA/ ROCK pathway in this process
Summary
Intervertebral disc degeneration is a main cause of low back pain which often results in disability and productivity limitation around the world [1]. According to previous studies on mechanical biology of disc cells, it is known that intracellular calcium ion and cytoskeletal remodeling are involved in the response of disc cells to mechanical stimulation, which may further regulate cell viability, gene expression, and posttranslational biosynthesis [7]. Most of these kinds of studies mainly focus on biological responses of NP cells to mechanical load, whereas mechanical biology of AF cells remains unclear. 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. This study provides us a deeper understanding on the AF cell’s behavior under mechanical stretch
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
