Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore, Singapore.
Eur Spine J. 2018 Oct;27(10):2621-2630. doi: 10.1007/s00586-018-5688-8. Epub 2018 Jul 2.
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.
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.
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.
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. These slides can be retrieved under Electronic Supplementary Material.
卧床休息时间延长和太空中的微重力会导致椎间盘（IVD）退化。然而，其潜在的分子机制尚不完全清楚。瞬时受体电位经典（TRPC）通道参与了几种组织的机械感觉，但在 IVD 中研究甚少。
取自手术活检的原代人 IVD 细胞，由纤维环和髓核组成（第 1-2 代），分别暴露于模拟微重力和 TRPC 通道抑制剂 SKF-96365（SKF）中，最长达 5 天。分析增殖能力、细胞周期分布、衰老和 TRPC 通道表达。
模拟微重力和 TRPC 通道拮抗均降低了 IVD 细胞的增殖能力并诱导衰老。虽然 SKF 处理后细胞周期分布发生显著变化（G1 减少，G2/M 增加），但模拟微重力 3 天后影响较小。最后，模拟微重力下 TRPC6 的表达下调。
模拟微重力和 TRPC 通道抑制均导致增殖减少和衰老增加。此外，模拟微重力降低了 TRPC6 的表达。因此，IVD 细胞衰老和机械转导可能受 TRPC6 表达的调节。本研究因此揭示了有前途的研究靶点。这些幻灯片可在电子补充材料中检索。
