Alfredo Franco-Obregon, Elena Cambria, Helen Greutert, Timon Wernas, Wolfgang Hitzl, Marcel Egli, Miho Sekiguchi, Norbert Boos, Oliver Hausmann, Stephen J. Ferguson, Hiroshi Kobayashi, Karin Würtz-Kozak
- Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity.Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies.…
MetadatenAuthor details: | Alfredo Franco-ObregonORCiD, Elena Cambria, Helen Greutert, Timon Wernas, Wolfgang HitzlORCiD, Marcel Egli, Miho Sekiguchi, Norbert Boos, Oliver Hausmann, Stephen J. FergusonORCiD, Hiroshi Kobayashi, Karin Würtz-KozakORCiDGND |
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DOI: | https://doi.org/10.1007/s00586-018-5688-8 |
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ISSN: | 0940-6719 |
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ISSN: | 1432-0932 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29968164 |
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Title of parent work (English): | European Spine Journal |
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Publisher: | Springer |
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Place of publishing: | New York |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/07/02 |
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Publication year: | 2018 |
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Release date: | 2021/09/20 |
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Tag: | Gene expression; Intervertebral disc; Mechanotransduction; Senescence; Simulated microgravity; TRP channels |
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Volume: | 27 |
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Issue: | 10 |
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Number of pages: | 10 |
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First page: | 2621 |
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Last Page: | 2630 |
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Funding institution: | Swiss National Science FoundationSwiss National Science Foundation (SNSF) [SNF PP00P2_163678/1]; Spine Society of Europe [Eurospine 2016_4] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Publishing method: | Open Access / Hybrid Open-Access |
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License (German): | CC-BY - Namensnennung 4.0 International |
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