Unraveling the role of mechanical cross-talk in the bone-cartilage unit in degenerative joint disease: an in silico multi-scale adaptive modeling approach

Osteoarthritis (OA) is a disease of the whole joint, with a progressive deterioration of cartilage and subchondral bone. Altered mechanical loading is widely accepted, but poorly understood as a driver of OA. Bone and cartilage are mechano-adaptive tissues. It has been assumed that changes in structural and material properties in either tissue caused by altered load distribution, drive mechano-adaptive response adaptations in the other tissue. This is called mechanical crosstalk in the bone-cartilage unit.  Animal experiments alone are not sufficient to elucidate dynamic mechanical crosstalk in OA. Our project aims to assess how mechano-adaptive interactions between bone and cartilage contribute to OA development. Our innovative approach relies on an adaptive, multi-scale computational modeling framework that relates estimates of joint loading (organ scale) to tissue loading (tissue scale), and dynamically adapt bone and cartilage based on local mechanical stimuli (adaptive model). First, we will assess knee loading in rats with destabilization of the medial meniscus (DMM) with multibody dynamics. Second, we will develop a multi-scale, adaptive model of the rat knee using finite element analysis, relating tissue mechanical cues to bone and cartilage mechano-regulatory algorithms, to predict joint adaptation in rats with DMM.  Third, we will use this model to predict joint adaptation when either bone resorption or cartilage degeneration is reduced.