Malone Amanda M D, Anderson Charles T, Tummala Padmaja, Kwon Ronald Y, Johnston Tyler R, Stearns Tim, Jacobs Christopher R
Palo Alto Veterans Administration Medical Center, Palo Alto, CA 94304, USA.
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13325-30. doi: 10.1073/pnas.0700636104. Epub 2007 Aug 2.
Primary cilia are sensory organelles that translate extracellular chemical and mechanical cues into cellular responses. Bone is an exquisitely mechanosensitive organ, and its homeostasis depends on the ability of bone cells to sense and respond to mechanical stimuli. One such stimulus is dynamic fluid flow, which triggers biochemical and transcriptional changes in bone cells by an unknown mechanism. Here we report that bone cells possess primary cilia that project from the cell surface and deflect during fluid flow and that these primary cilia are required for osteogenic and bone resorptive responses to dynamic fluid flow. We also show that, unlike in kidney cells, primary cilia in bone translate fluid flow into cellular responses in bone cells independently of Ca(2+) flux and stretch-activated ion channels. These results suggest that primary cilia might regulate homeostasis in diverse tissues by allowing mechanical signals to alter cellular activity via tissue-specific pathways. Our identification of a mechanism for mechanotransduction in bone could lead to therapeutic approaches for combating bone loss due to osteoporosis and disuse.
初级纤毛是一种感觉细胞器，可将细胞外化学和机械信号转化为细胞反应。骨骼是一种对机械刺激极其敏感的器官，其稳态取决于骨细胞感知和响应机械刺激的能力。一种这样的刺激是动态流体流动，它通过未知机制触发骨细胞中的生化和转录变化。在这里，我们报告骨细胞拥有从细胞表面伸出并在流体流动期间发生偏转的初级纤毛，并且这些初级纤毛是对动态流体流动的成骨和骨吸收反应所必需的。我们还表明，与肾细胞不同，骨中的初级纤毛将流体流动转化为骨细胞中的细胞反应，而与Ca(2+)通量和拉伸激活离子通道无关。这些结果表明，初级纤毛可能通过允许机械信号通过组织特异性途径改变细胞活性来调节不同组织中的稳态。我们对骨中机械转导机制的鉴定可能会导致对抗因骨质疏松症和废用引起的骨质流失的治疗方法。
