Mechanotransduction in human bone: in vitro cellular physiology that underpins bone changes with exercise.

Bone has a remarkable ability to adjust its mass and architecture in response to a wide range of loads, from low-level gravitational forces to high-level impacts. A variety of types and magnitudes of mechanical stimuli have been shown to influence human bone cell metabolism in vitro, including fluid shear, tensile and compressive strain, altered gravity and vibration. Therefore, the current article aims to synthesize in vitro data regarding the cellular mechanisms underlying the response of human bone cells to mechanical loading. Current data demonstrate commonalities in response to different types of mechanical stimuli on the one hand, along with differential activation of intracellular signalling on the other. A major unanswered question is, how do bone cells sense and distinguish between different types of load? The studies included in the present article suggest that the type and magnitude of loading may be discriminated by overlapping mechanosensory mechanisms including (i) ion channels; (ii) integrins; (iii) G-proteins; and (iv) the cytoskeleton. The downstream signalling pathways identified to date appear to overlap with known growth factor and hormone signals, providing a mechanism of interaction between systemic influences and the local mechanical environment. Finally, the data suggest that exercise should emphasize the amount of load rather than the number of repetitions.