TY  - JOUR
A1  - Franco-Obregon, Alfredo
A1  - Cambria, Elena
A1  - Greutert, Helen
A1  - Wernas, Timon
A1  - Hitzl, Wolfgang
A1  - Egli, Marcel
A1  - Sekiguchi, Miho
A1  - Boos, Norbert
A1  - Hausmann, Oliver
A1  - Ferguson, Stephen J.
A1  - Kobayashi, Hiroshi
A1  - Würtz-Kozak, Karin
T1  - TRPC6 in simulated microgravity of intervertebral disc cells
JF  - European Spine Journal
N2  - 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.
KW  - Intervertebral disc
KW  - Simulated microgravity
KW  - Senescence
KW  - TRP channels
KW  - Mechanotransduction
KW  - Gene expression
Y1  - 2018
U6  - https://doi.org/10.1007/s00586-018-5688-8
SN  - 0940-6719
SN  - 1432-0932
VL  - 27
IS  - 10
SP  - 2621
EP  - 2630
PB  - Springer
CY  - New York
ER  -