Dynamics of Osteocyte Embedding and Differentiation and the Fate of Osteocytes after Bone Resorption

Abstract

The differentiation of an osteoblast into an osteocyte is a complex process involving arrest of cell motility, embedding into osteoid matrix, transformation to a dendritic morphology, interconnection of the dendrites with established osteocytes and entrapment of the new osteocyte within a mineralized matrix, all of which are accompanied by characteristic gene expression changes. To gain new insight into these processes, our laboratory has performed live‐cell and intravital imaging using transgenic reporter mice with fluorescently tagged osteocytes, osteoblasts and/or osteoclasts and GFP‐tagged collagen. This work has revealed the highly dynamic nature of the osteocyte embedding and differentiation process, it’s integration with ECM assembly and mineralization and has identified three apparent mechanisms for osteocyte embedding in collagen. Dual imaging of osteoclast resorption and osteocyte dynamics revealed that the predominant fate of osteocytes following bone resorption is to undergo cell death. These live imaging studies are providing novel insights into the properties, differentiation and function of osteocytes and the fate of osteocytes during bone resorption and enable quantitation of these cell dynamics in their natural bone environment in healthy and diseased states.