The hypothesis that mechanical loading induced signals are transmitted and integrated by a connected cellular network (CCN) before reaching bone surfaces where adaptation occurs is investigated in this study. Our objective is to develop a computational connected cellular network (CCCN) model to explore how bone cells transmit the signals through intercellular communication. The intercellular communication signal is selected as the bone fluid shear stress induced by bending and axial loading in transverse sections of avian long bones in two animal adaptation experiments (Gross et al. J Bone Miner Res 12:​982-988, 1997 and Judex et al. J Bone Miner Res 12:​1737-1745, 1997). The distribution of the fluid shear stress is computed using a mathematical model based on the microstructure of the avian bones. The computed fluid shear stress is found to be correlated with the radial strain gradient obtained in the experiments. However, experimentally determined bone response shows no linear spatial correlation with the absolute value of averaged shear stress. These results suggest that the radial strain gradient is the driving force for bone fluid flow in the radially distributed lacunar-canalicular system and that bone formation is not linearly related to the loading induced local stimulus.

A CCCN model is developed to study the intercellular communication within a grid of bone cells by correlating bone adaptation responses in the experiments with the computed fluid shear stress. Intercellular communication patterns extracted by adjusting cell sensitivities (loading and signal thresholds) and connection weights indicate the cell population responsible for perceiving the loading induced signal and regulating bone formation in the CCCNs. The averaged cell sensitivities and connection weights are shown to be inversely correlated with the averaged fluid shear stress across the bone section. Network results suggest that the loading threshold play an important role in regulating the bone response. The proposed CCCN model provides a unique and important tool to analyze intercellular communication and to discover the underlying relationship between input and output data in biological structures.