Abstract
Recently, a dysregulation of the Hippo-YAP/TAZ pathway has been correlated with intervertebral disc (IVD) degeneration (IDD), as it plays a key role in cell survival, tissue regeneration, and mechanical stress. We aimed to investigate the influence of different mechanical loading regimes, i.e., under compression and torsion, on the induction and progression of IDD and its association with the Hippo-YAP/TAZ pathway. Therefore, bovine IVDs were assigned to one of four different static or complex dynamic loading regimes: (i) static, (ii) “low-stress”, (iii) “intermediate-stress”, and (iv) “high-stress” regime using a bioreactor. After one week of loading, a significant loss of relative IVD height was observed in the intermediate- and high-stress regimes. Furthermore, the high-stress regime showed a significantly lower cell viability and a significant decrease in glycosaminoglycan content in the tissue. Finally, the mechanosensitive gene CILP was significantly downregulated overall, and the Hippo-pathway gene MST1 was significantly upregulated in the high-stress regime. This study demonstrates that excessive torsion combined with compression leads to key features of IDD. However, the results indicated no clear correlation between the degree of IDD and a subsequent inactivation of the Hippo-YAP/TAZ pathway as a means of regenerating the IVD.
Highlights
Intervertebral disc (IVD) degeneration (IDD) is a leading cause of chronic low back pain (LBP) [1]
It is assumed that a close interplay between mechanical overloading, catabolic cell response and the degeneration of the IVD’s extracellular matrix (ECM) form a vicious circle that leads to the inevitable progression of IDD [2]
After one week in the bioreactor, a significant loss (p < 0.0001) of the absolute height was recorded in every mechanical loading regime tested (Figure 1a)
Summary
Intervertebral disc (IVD) degeneration (IDD) is a leading cause of chronic low back pain (LBP) [1]. Risk factors that may favour the initiation and progression of IDD include trauma [3], smoking [4,5], genetic factors [6,7], and mechanical stress [8,9]. It is assumed that a close interplay between mechanical overloading, catabolic cell response and the degeneration of the IVD’s extracellular matrix (ECM) form a vicious circle that leads to the inevitable progression of IDD [2]. The first signs of IDD are usually observed in the IVD’s core tissue, known as the nucleus pulposus (NP) [10].
Sign-in/Register to view highlights & summary 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.
