Primary cilia act as microgravity sensors by depolymerizing microtubules to inhibit osteoblastic differentiation and mineralization
Primary cilia act as microgravity sensors by depolymerizing microtubules to inhibit osteoblastic differentiation and mineralization
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初级纤毛通过解聚微管来抑制成骨细胞分化和矿化，充当微重力传感器
DOI：
10.1016/j.bone.2020.115346
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发表时间：
2020-07-01
期刊：
影响因子：
4.1
通讯作者：
Wang, Jufang
中科院分区：
文献类型：
--
作者：
Shi, Wengui;Zhang, Yanan;Wang, Jufang
微重力引起的骨骼退化是长期太空飞行中的一个主要挑战，因为其潜在机制仍然难以捉摸。此前，我们报道了成骨细胞的初级纤毛在微重力条件下逐渐消失，纤毛的消失对于抑制微重力诱导的成骨是必要的。然而，初级纤毛的确切作用尚未完全阐明。在这里，我们报告微重力可逆地解聚大鼠颅骨成骨细胞（ROB）的微管网络，但对肌动蛋白丝的结构没有影响。通过水合氯醛或针对鞭毛内转运蛋白 88 (IFT88) 的小干扰 RNA 序列 (siRNA) 来防止初级纤毛发生，可有效缓解微重力诱导的微管解聚，而使用药理学方法稳定微管并不能防止初级纤毛在微重力条件下消失。此外，对从纤毛基体出现的微管数量进行量化表明，微重力显着减少了基底微管的数量，这取决于初级纤毛的存在。最后，微重力诱导的 ROB 分化、成熟和矿化抑制通过细胞质微管的稳定而消除。综上所述，这些数据表明，初级纤毛依赖性微管解聚是抑制微重力诱导的成骨的原因。我们的研究提供了关于微重力引起的骨质流失机制的新视角，支持了先前确立的初级纤毛作为骨代谢传感器的作用。
Microgravity-induced bone deterioration is a major challenge in long-term spaceflights since the underlying mechanisms remain elusive. Previously, we reported that primary cilia of osteoblasts gradually disappeared in microgravity conditions, and cilia abrogation was necessary for the inhibition of osteogenesis induced by microgravity. However, the precise roles of primary cilia have not been fully elucidated. Here, we report that microgravity depolymerizes the microtubule network of rat calvarial osteoblasts (ROBs) reversibly but has no effect on the architecture of actin filaments. Preventing primary ciliogenesis by chloral hydrate or a small interfering RNA sequence (siRNA) targeting intraflagellar transport protein 88 (IFT88) effectively relieves microgravity-induced microtubule depolymerization, whereas the stabilization of microtubules using pharmacological approaches cannot prevent the disappearance of primary cilia in microgravity conditions. Furthermore, quantification of the number of microtubules emerging from the ciliary base body shows that microgravity significantly decreases the number of basal microtubules, which is dependent on the existence of primary cilia. Finally, microgravity-induced repression of the differentiation, maturation, and mineralization of ROBs is abrogated by the stabilization of cytoplasmic microtubules. Taken together, these data suggest that primary cilia-dependent depolymerization of microtubules is responsible for the inhibition of osteogenesis induced by microgravity. Our study provides a new perspective regarding the mechanism of microgravity-induced bone loss, supporting the previously established role of primary cilia as a sensor in bone metabolism.