Studying osteocytes within their environment.

It is widely hypothesized that osteocytes are the mechano-sensors residing in the bone's mineralized matrix which control load induced bone adaptation. Owing to their inaccessibility it has proved challenging to generate quantitative in vivo experimental data which supports this hypothesis. Recent advances in in situ imaging, both in non-living and living specimens, have provided new insights into the role of osteocytes in the skeleton. Combined with the retrieval of biochemical information from mechanically stimulated osteocytes using in vivo models, quantitative experimental data is now becoming available which is leading to a more accurate understanding of osteocyte function. With this in mind, here we review i) state of the art ex vivo imaging modalities which are able to precisely capture osteocyte structure in 3D, ii) live cell imaging techniques which are able to track structural morphology and cellular differentiation in both space and time, and iii) in vivo models which when combined with the latest biochemical assays and microfluidic imaging techniques can provide further insight on the biological function of osteocytes.