Croft, Andreas S.; Roth, Ysaline; Oswald, Katharina A. C.; Corluka, Slavko; Bermudez-Lekerika, Paola; Gantenbein, Benjamin (2021). In Situ Cell Signalling of the Hippo-YAP/TAZ Pathway in Reaction to Complex Dynamic Loading in an Intervertebral Disc Organ Culture. International journal of molecular sciences, 22(24) MDPI 10.3390/ijms222413641
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
09 Interdisciplinary Units > Microscopy Imaging Center (MIC) 04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Croft, Andreas Shaun, Oswald, Katharina Anna Christine, Corluka, Slavko, Bermudez, Paola, Gantenbein, Benjamin |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1422-0067 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Benjamin Gantenbein |
Date Deposited: |
17 Jan 2022 15:54 |
Last Modified: |
04 Feb 2024 11:04 |
Publisher DOI: |
10.3390/ijms222413641 |
PubMed ID: |
34948441 |
BORIS DOI: |
10.48350/162834 |
URI: |
https://boris.unibe.ch/id/eprint/162834 |
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