Bone mechanobiology in mice: toward single-cell in vivo mechanomics

Mechanically driven bone (re)modeling is a multiscale process mediated through complex interactions between multiple cell types and their microenvironments. However, the underlying mechanisms of how cells respond to mechanical signals are still unclear and are at the focus of the field of bone mechanobiology. Traditionally, this complex process has been addressed by reducing the system to single scales and cell types. It is only recently that more integrative approaches have been established to study bone mechanobiology across multiple scales in which mechanical load at the organ level is related to molecular responses at the cellular level. The availability of mouse loading models and imaging techniques with improved spatial and temporal resolution has made it possible to track dynamic bone (re)modeling at the tissue and cellular level in vivo. Coupled with advanced computational models, the (re)modeling activities at the tissue scale can be associated with the mechanical microenvironment. However, methods are lacking to link the molecular responses of different cell types to their local mechanical microenvironment and bone (re)modeling activities occurring at the tissue scale. With recent improvements in "omics" technologies and single-cell molecular biology, it is now possible to sequence the complete genome and transcriptome of single cells. These technologies offer unique opportunities to comprehensively investigate the cellular transcriptional profiles within their specific microenvironment. By combining single-cell "omics" technologies with well-established tissue-scale models of bone mechanobiology, we propose a mechanomics approach to locally analyze the transcriptome of single cells with respect to their local 3D mechanical in vivo environment.