title: A multiscale framework based on the physiome markup languages for exploring the initiation of osteoarthritis at the bone-cartilage interface.
abstract: The initiation of osteoarthritis (OA) has been linked to the onset and progression of pathologic mechanisms at the cartilage-bone interface. Most importantly, this degenerative disease involves cross-talk between the cartilage and subchondral bone environments, so an informative model should contain the complete complex. In order to evaluate this process, we have developed a multiscale model using the open-source ontologies developed for the Physiome Project with cartilage and bone descriptions at the cellular, micro, and macro levels. In this way, we can effectively model the influence of whole body loadings at the macro level and the influence of bone organization and architecture at the micro level, and have cell level processes that determine bone and cartilage remodeling. Cell information is then passed up the spatial scales to modify micro architecture and provide a macro spatial characterization of cartilage inflammation. We evaluate the framework by linking a common knee injury (anterior cruciate ligament deficiency) to proinflammatory mediators as a possible pathway to initiate OA. This framework provides a "virtual bone-cartilage" tool for evaluating hypotheses, treatment effects, and disease onset to inform and strengthen clinical studies.
authors: Auckland Bioengineering Institute, Auckland 1010, New Zealand. v.shim@auckland.ac.nz
authors: Vickie B
authors: VB
authors: Shim
authors: Peter J
authors: PJ
authors: Hunter
authors: Peter
authors: P
authors: Pivonka
authors: Justin W
authors: JW
authors: Fernandez
mesh_terms: D016118:Anterior Cruciate Ligament / Q000473:pathology; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D019295:Computational Biology / Q000379:methods*; D020342:Finite Element Analysis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008954:Models, Biological; D010003:Osteoarthritis / Q000473:pathology*; D011381:Programming Languages