Cellular and molecular mechanotransduction in bone

This chapter reviews the state of knowledge with respect to skeletal mechanobiology. Forms of tissue-level mechanical stimulation are first described, including electromagnetic fields, strain, fluid flow, vibration, and damage. The resulting biophysical environment at the cellular and pericellular level is also considered. However, for a biological response to occur in response to loading, mechanical signals must induce cellular biochemical signaling. How bone and progenitor cells may sense their mechanical environment is addressed by describing potential candidates for molecular transduction of mechanical to biochemical signaling. Candidates include cytoskeletal proteins, integrins and adhesion-associated proteins, membrane channels, plasma membrane dynamics, mechanosomes, and primary cilia. Furthermore, mechanically activated intracellular signaling pathways involving calcium, G-proteins, and kinases, as well as cell-cell pathways involving gap junctions, nitric oxide, eicosanoids, CXCL12, and nucleotides are discussed. Progress toward understanding mechanisms involved in bone mechanotransduction holds great potential in providing therapeutic targets to the disease of osteoporosis.