Skeletal Mechanobiology

Skeletal tissue is a reservoir of calcium that is important for proper muscle and nerve function, and houses the marrow that supports the hematopoietic and mesenchymal stem cell niche. The skeleton also provides the framework of the body, supports organs and tissues against gravitational force, provides levers through which muscles act to aid in locomotion, and protects internal organs against blunt force trauma. For a seemingly inert tissue, bone has the ability to remodel, 282reorganize, and regenerate in response to mechanical loading and injury. Mechanical force is an important regulator of biology and plays a critical role in tissue development and maintenance. ¹ Indeed, mechanical loading is a potent regulator of bone turnover, and the structural success of the skeleton is due in large part to the capacity of bones to respond to the prevailing mechanical environment by optimizing its shape and size to meet physical demands. ² Mechanisms by which mechanical loading regulates bone remodeling and adaptation involve first, the sensing of an extracellular physical signal, and second, the conversion of this signal into a biochemical response, a process known as mechanotransduction. The purpose of this chapter is to systematically review the state of knowledge with respect to skeletal mechanobiology. After a brief outline of basic bone physiology, we review the research on the ability of bone cells to sense and to respond to physical signals and the nature of the physical signals experienced at a cellular level. Finally, we consider potential molecular mechanisms responsible for cellular mechanosensing and some recently uncovered novel mechanisms.