In Vitro Models to Study Endochondral Ossification

Endochondral ossification is a critical process in bone formation and regeneration whereby a cartilage template is gradually remodelled into mature bone during development. This process is recapitulated during healing/fracture repair. Understanding and modelling endochondral ossification is relevant not only for tissue engineering/regenerative medicine (TERM)-based approaches to bone defect repair. A wide range of diseases somehow involve bone formation, repair or disturbed homeostasis, usually via endochondral ossification. For example, osteoarthritis, cancer metastasis, leukaemia and diseases involving ectopic calcification, such as heterotopic ossification and even some aspects of atherosclerosis are intrinsically linked with endochondral ossification. Despite this, there is a huge lack of humanised in vitro and in vivo models of endochondral ossification and ectopic calcification. One of the reasons for this is the exceptional cellular and tissue complexity found in our bones. There are a huge number of cell and tissue types found in our long bones making it difficult to model bone in vitro . However, it is clear that animal models, while having a huge role to play in biological research for many years to come, cannot always fully recapitulate the complexity or specificity of human physiology. The ability to model endochondral ossification in vitro using human derived cells would offer avenues to investigate many of the most debilitating and costly diseases in the word today. Here we present our current progress in developing models of endochondral ossification in vitro to increase our understanding and control of this process. We combine multiple cell types in 3D to recapitulate several of the critical processes necessary for endochondral ossification and demonstrate our preliminary work in applying this work to the study of cancer metastasis.