The effect of osteocyte apoptosis on signalling in the osteocyte and bone lining cell network: a computer simulation

Abstract

Osteocytes play a critical role in the regulation of bone remodelling by translating strain due to mechanical loading into biochemical signals transmitted through the interconnecting lacuno-canalicular network to bone lining cells (BLCs) on the bone surface. This work aims to examine the effects of disruption of that intercellular communication by simulation of osteocyte apoptosis in the bone matrix. A model of a uniformly distributed osteocyte network has been developed that simulates the signalling through the network to the BLCs based on strain level. Bi-directional and asymmetric communication between neighbouring osteocytes and BLCs is included. The effect of osteocyte apoptosis is examined by preventing signalling at and through the affected cells. The simulation shows that apoptosis of only 3% of the osteocyte cells leads to a significant reduction in the peak signal at the BLCs. Furthermore, experiments with the model confirm how important the location and density of the apoptotic osteocytes are to the signalling received at the bone surface. With 5% and 9% osteocyte apoptosis, the mean peak BLC levels were reduced by 25% and 37% respectively. Such a significant reduction in the signal at the BLCs may explain a possible mechanism that leads to the increased remodelling and eventual bone loss observed with osteoporosis. More generally, it provides a unique framework for a broader exploration of the role of osteocyte and bi-directional and asymmetric cell-cell communication in mechanotransduction, and the effects of disruption to that communication.