Cells are exquisitely sensitive and adaptive to changes in environment. Within the mammalian skeleton, routine activity creates an array of biophysical forces on bone cells. Cells that perceive and respond to these forces initiate intracellular signaling cascades designed to alter cell metabolism or phenotype to maintain or alter bone mass and architecture. Perceiving an altered biophysical environment and altering cell function is termed mechanotransduction. Understanding the mechanotransduction processes that enable cells to perceive an altered extracellular environment not only is critical for a systems-level biologic approach but may also provide the foundation for treating diseases of bone loss, such as senile osteoporosis. Osteocytes may play a crucial role in mechanotransduction because of their localization and plenitude within bone matrix; further, dendritic processes enable intercellular connectivity to neighboring osteocytes, osteoblasts, osteoclasts, and stem cells present within the marrow and periosteum. In vitro models for mechanical loading have begun to identify cellular responses to biophysical forces like fluid flow; chemical antagonists, siRNA, or cells from knockout animals have enabled investigators to delineate the contribution of specific proteins or signaling cascades to a particular response, increases in cytosolic calcium levels, or induction of a particular candidate gene. One of the earliest measurable responses to a biophysical force is activation of an ion channel in the plasma membrane. Within this chapter, we review evidence for ion channel activation within bone, including common optical imaging methods, the role of these ion channels in skeletal mechanotransduction in vitro, and in vivo evidence either corroborating or refuting in vitro findings.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)