"Whither flows the fluid in bone?" An osteocyte's perspective.

Bone represents a porous tissue containing a fluid phase, a solid matrix, and cells. Movement of the fluid phase within the pores or spaces of the solid matrix translates endogenous and exogenous mechanobiological, biochemical and electromechanical signals from the system that is exposed to the dynamic external environment to the cells that have the machinery to remodel the tissue from within. Hence, bone fluid serves as a coupling medium, providing an elegant feedback mechanism for functional adaptation. Until recently relatively little has been known about bone fluid per se or the influences governing the characteristics of its flow. This work is designed to review the current state of this emerging field. The structure of bone, as an environment for fluid flow, is discussed in terms of the properties of the spaces and channel walls through which the fluid flows and the influences on flow under physiological conditions. In particular, the development of the bone cell syncytium and lacunocanalicular system are presented, and pathways for fluid flow are described from the systemic to the organ, tissue, cellular and subcellular levels. Finally, exogenous and endogenous mechanisms for pressure-induced fluid movement through bone, including mechanical loading, vascular derived pressure gradients, and osmotic pressure gradients are discussed. The objective of this review is to survey the current understanding of the means by which fluid flow in bone is regulated, from the level of the skeletal system down to the level of osteocyte, and to provide impetus for future research in this area of signal transduction and coupling. An understanding of this important aspect of bone physiology has profound implications for restoration of function through innovative treatment modalities on Earth and in space, as well as for engineering of biomimetic replacement tissue.