Imaging the Dynamics of Bone Elongation: Integrating Macro‐ and Micro‐scale Processes at the Organ Level in situ

Knowledge of variables associated with endochondral ossification has been based on synthesizing observations from multiple sources: clinical abnormalities of long bone growth; physiologically‐based whole animal experiments; chondrocytic biochemistry/physiology; and molecular analyses including murine models with genetic manipulations. Molecular approaches have been particularly robust at enumerating the panoply of players potentially involved, but the challenge remains of understanding the role of these players in an organ level system of an animal growing through time. Live animal imaging offers the potential to maintain the organ‐level environment of the growth plate for functional analysis of the real‐time complexity of movement of potential regulatory molecules within the extracellular matrix, communication links among chondrocytes, and interactions of chondrocytes with cells in adjacent bone, vasculature, and perichondrium. This approach can be extended by manipulating other complex variables known to affect the rate and extent of postnatal bone elongation such as nutritional status, exercise status, or any of a variety of genetic changes resulting in compromised elongation and abnormal stature. Thus imaging in situ has the potential to return analyses of growth plate regulation to its organ‐level environment and to answer questions of possible value for therapeutic discovery.