Healthy bones combine a proper resistance against fracture with a minimum use of material. This property is likely brought about by osteocytes in response to mechanical cues, but it is still unknown how whole bone loads are translated into a signal that can be sensed by the osteocytes. The goal of this chapter is to critically analyze our current knowledge on how bone transduction takes place from the level of mechanical loads placed upon the bone as an organ to activation of a cell.Bone is constantly remodeled by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. The balance between bone resorption and bone formation determines whether the process of bone remodeling leads to a net gain or loss of bone mass. The number and activity of osteoclasts and osteoblasts are determined by a multitude of factors, such as hormones and cytokines, as well as by locally produced signaling molecules [1-6]. The major source of signaling molecules in bone is likely the osteocytes, which comprise over 90% of the entire bone cell population. Osteocytes are stellate cells, which are embedded within the calcified bone matrix. They form a high number of cell-cell contacts through their long slender cell processes, forming a syncytium capable of rapid transduction of signals. Osteocytes are highly mechanosensitive and alter the production of a multitude of signaling molecules when triggered with a mechanical stimulus, enabling them to locally affect osteoblast and osteoclast activity [7-10]. These properties of the osteocytes not only facilitate the adaptation of bone mass but, importantly, also allow the adaptation of trabecular bone architecture according to the demands of mechanical usage [11,12].Years ago, it has been shown that isolated osteocytes show a stronger response to a mechanical stimulation in the form of a fluid flow than osteoblasts or periosteal fibroblasts [13]. In vivo models, including strained cores of adult dog cancellous bone, embryonic chicken tibiotarsi, mouse ulnae, rat caudal vertebrae, and rat tibiae, as well as experimental tooth movement in rats, have demonstrated that osteocytes in intact bone change their enzyme activity and RNA synthesis rapidly after mechanical loading [14][15][16][17][18][19]. These studies showed that bone loading produces rapid changes in metabolic activity of osteocytes and suggested that osteocytes may indeed function as mechanosensors in bone. A more recent ground-breaking study by Tatsumi et al. [20] showed that the loss of bone following hind limb unloading of mice was prevented when 80% of the osteocytes were ablated, demonstrating that osteocytes not only sense whole bone loads but are also essential transducers of mechanical signals within bone.
Bone Fluid Flow TheoryIf we accept that osteocytes are the professional mechanosensing cells of bone, then how do these cells sense