• Alfredo Franco-Obregón, Elena Cambria, Helen Greutert, Timon Wernas, Wolfgang Hitzl, Marcel Egli, Miho Sekiguchi, Norbert Boos, Oliver Hausmann, Stephen J Ferguson, Hiroshi Kobayashi, and Karin Wuertz-Kozak.
• Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
• Eur Spine J. 2018 Oct 1; 27 (10): 2621-2630.

PurposeProlonged 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.MethodsPrimary 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 5 days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed.ResultsBoth 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 3 days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity.ConclusionsSimulated 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. These slides can be retrieved under Electronic Supplementary Material.

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