Application of Stochastic Network Models for the Study of Molecular Transport Processes in Bone

Osteocytes are the most abundant cells in bone. They are entombed in lacunae within the bone matrix, but are interconnected via their processes that run within the canaliculi with other osteocytes, as well as with the osteoblasts and bone lining cells on the bone surfaces, and thus from a cellular syncytium. However, the osteocytes are not immediately connected with the vasculature of bone, which means that the transport of nutrients and hormones to the cells and the removal of waste products from the cells, as well as transport of signaling molecules between the cells, has to occur either via the pericellular fluid spaces in the lacunocanalicular network, via the matrix micropores between the collagen fibers and the apatite crystals, or via intracellular transport mechanisms. Only recently our laboratory and other research groups have started to examine the transport pathways of different molecular size substances within bone systematically, using experimental tracer methods (e.g. [1, 7]). These experiments have unveiled the molecular sieving characteristics of bone: While small tracers with molecular weights of 300 Daltons (Da, e.g. glucose and small amino acids) are found in abundance throughout the bone matrix and the lacunocanalicular network, larger molecules (e.g. cytokines and serum derived proteins) are only transported through the pericellular spaces of the lacunocanalicular network. Furthermore, the transport of these substances through the lacunocanalicular network can be enhanced by mechanical loading of bone [1]. These findings highlight the importance of the lacunocanalicular network for the survival of the osteocytes and thereby tissue health. However, the state of the osteocyte syncytium is affected by age and bone diseases. It has been shown that the number of osteocytes in cortical bone decreases with age [6]. Furthermore, a histological study of cortical bone tissue samples from donors undergoing hip replacement surgery has shown that the morphology of the lacunocanalicular network is altered in diseased bone [2].