Bone as an ion exchange system: evidence for a link between mechanotransduction and metabolic needs. Am J Physiol Endocrinol Metab 282: E851-E864, 2002. First published November 20, 2001 10.1152/ajpendo.00367.2001.-To detect whether the mutual interaction occurring between the osteocytes-bone lining cells system (OBLCS) and the bone extracellular fluid (BECF) is affected by load through a modification of the BECF-extracellular fluid (ECF; systemic extracellular fluid) gradient, mice metatarsal bones immersed in ECF were subjected ex vivo to a 2-min cyclic axial load of different amplitudes and frequencies. The electric (ionic) currents at the bone surface were measured by a vibrating probe after having exposed BECF to ECF through a transcortical hole. The application of different loads and different frequencies increased the ionic current in a dosedependent manner. The postload current density subsequently decayed following an exponential pattern. Postload increment's amplitude and decay were dependent on bone viability. Dummy and static loads did not induce current density modifications. Because BECF is perturbed by loading, it is conceivable that OBLCS tends to restore BECF preload conditions by controlling ion fluxes at the boneplasma interface to fulfill metabolic needs. Because the electric current reflects the integrated activity of OBLCS, its evaluation in transgenic mice engineered to possess genetic lesions in channels or matrix constituents could be helpful in the characterization of the mechanical and metabolic functions of bone.osteocytes; bone lining cells; mineral homeostasis; mechanical loading; fluid shear stress THE MUTUAL INTERACTION occurring between the osteocyte-bone lining cell system (OBLCS) and the surrounding bone extracellular fluid (BECF) has been suggested to play a pivotal role in bone mechanotransduction (3, 37). OBLCS is constituted by a network of stellate cells buried within the bone matrix, the osteocytes, having an asymmetrical arborization of dendrites polarized toward the bone surfaces, where they come into contact with the bone lining cells or the osteoblasts according to whether the bone is in a resting or a growing phase, respectively. Because the cells forming such a three-dimensional protoplasmic network are all joined by gap junctions, OBLCS actually constitutes a functional syncytium (24,27,26). The lacuno and canalicular network of cavities, enclosing the osteocyte cell bodies and dendrites, forms within the bone matrix a complex microstructure of pores and channels filled by BECF that has a different ionic composition from the systemic extracellular fluid (ECF) of the perivascular loose connective tissue surrounding the bone surfaces.This ionic difference is maintained by a pump-leak system that selectively operates at the OBLCS level (32, 33, 34) as a partition system (4) generating an ionic gradient between BECF and ECF (21, 22, 23, 30) with a subsequent electric potential difference at the bone membrane (36) that appears to be under parathyroid hormone control (2...
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