A Systems Approach to Bone Remodeling & Mechanotransduction

Abstract

A systems-level computational modeling approach is implemented to study the mechano-regulation of bone at cellular level. Issues addressed include determining the intra-cellular response of bone cells to mechanical stimulus, bone response to different mechanical loading conditions, the role of intra-cellular feedback regulation in bone remodeling, and the link between reduced mechanical loading and decreased bone mass. The salient features of this modeling technique include systems biology based network modeling, parameter estimation based on evolutionary computing, and control systems theory to model feedback in the signaling networks. The simulation studies indicate that the disruption of intra-cellular feedback regulation leads to decreased bone formation in osteoblasts and increased bone resorption in osteoclasts, causing low bone mass. Low bone mass is generally observed in reduced loading conditions. Hence, it is deduced that reduced mechanical loading leads to disruption in the feedback regulation to result in low bone mass. The results of these simulation studies are expected to serve as useful guidelines for planning relevant experimental work to study the effect of mechanical loading on bone at cellular level.