TRPC6 in simulated microgravity of intervertebral disc cells

TRPC6 in simulated microgravity of intervertebral disc cells

Alfredo Franco-Obregón, Elena Cambria, Helen Greutert, Timon Wernas, Wolfgang Hitzl, Marcel Egli, Miho Sekiguchi, Norbert Boos, Oliver Hausmann, Stephen J. Ferguson, Hiroshi Kobayashi, Karin Wuertz-Kozak

October 2018, Volume 27, Issue 10, pp 2621 - 2630
DOI
10.1007/s00586-018-5688-8
First Online: 02 July 2018
Abstract

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 5 days. 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 3 days 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.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.]