© Springer Science+Business Media Dordrecht 2012. Articular cartilage, like many other living tissues, experiences a complex physiological mechanical loading environment which regulates cell function and tissue homeostasis through a process of mechanotransduction. The underlying signalling pathways and mechanotransduction mechanisms are poorly understood but recent studies point to the involvement of a fascinating and previously over looked cellular organelle called the primary cilium. In other cell types, including epithelial cells and osteocytes, primary cilia have been shown to function as mechanoreceptors. This appears to involve deflection of the cilium in response to fluid shear forces which then activates calcium signalling pathways. In this chapter we examine the structure and function of the primary cilium and its potential role in mechanotransduction in articular chondrocytes. In particular we review exciting recent studies which suggest that the primary cilium mediates chondrocyte mechanotransduction through regulation of purinergic calcium signalling leading to changes in extracellular matrix synthesis. Furthermore we examine how other cilia-mediated mechanotransduction pathways, most notably hedgehog signalling, are also regulated by mechanical forces thereby controlling cell proliferation and tissue development. Finally we describe the regulation of primary cilia structure and how mechanical forces may influence the complex balance of cilia assembly and disassembly leading to alterations in cilia function. In summary this chapter explores the rapidly evolving area of primary cilia and their response to mechanical forces with a particular focus on articular cartilage for which mechanical loading is critical for homeostasis and functionality. Understanding the role of the primary cilium in mechanobiology will aid the development of novel therapeutic strategies for pathologies, such as osteoarthritis, that involve disruption of primary cilia function.
Mechanically Gated Channels and their Regulation
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