The role of connectivity and stochastic osteocyte behavior in the distribution of perilabyrinthine bone degeneration. A Monte Carlo based simulation study

Previous studies of undecalcified temporal bones labeled with fluorescent tissue time markers and basic fuchsine have documented the unique spatial and temporal patterns underlying inner ear bone development, morphology and degeneration, and has led to the identification of inner ear OPG as the candidate inhibiter of perilabyrinthine bone resorption. Resulting age related excessive matrix micro damage, osteocyte death and degeneration of the OPG signaling pathway is expected to trigger bone remodeling in the otic capsule, but when this happens the morphology of the remodeling bone is abnormal and the distribution is not entirely smooth and predictable, but rather multifocal and chaotic with a centripetal predilection at the window regions, as in otosclerosis. Based on the observed histological patterns, the fundamental preconditions of perilabyrinthine bone cell behavior can be deduced. When this information is used to generate a virtual computer representation of the cellular signaling network, the fate of the aging network can be studied by 'virtual histology' in any number of simulated 'individuals'. We demonstrate how a combination of simple osteocyte survival functions derived from histological observations and the effect of connectivity may account for gradual centripetal degeneration as well as occasional focal degeneration of the cellular anti resorptive signaling pathway around the fluid space of the inner ear and create a permissive environment for otosclerosis. (C) 2016 Elsevier B.V. All rights reserved.