Cell Signaling in Tenocytes: Response to Load and Ligands in Health and Disease.

Signaling in tenocytes during development, homeostasis and injury involves multiple and redundant pathways. Given that tendons transmit mechanical forces from muscle to bone to effect movement, a key function for tenocytes is the detection of and response to mechanical stimulation. Mechanotransduction involves matrix-integrin-cytoskeleton to nucleus signaling, gap junction intercellular communication, changes in intracellular calcium (Ca(2+)), activation of receptors and their pathways, and responses to biochemical factors such as hormones, growth factors, adenosine triphosphate (ATP) and its derivatives, and neuromodulators. The primary cilium also plays a key role in the detection of mechanical signals. During development, transforming growth factor-β (TGF-β), bone morphogenetic protein (BMP), and hedgehog (Hh) signaling modulate tendon differentiation and formation. The response to injury is complex and varied involving not only inflammatory mediators such as interleukin-1β but also mechanosensing. This chapter reviews the signaling pathways tenocytes use during mechanotransduction, development and in response to injury.