Using confocal imaging approaches to understand the structure and function of osteocytes and the lacunocanalicular network.

Abstract Although overlooked in the past, osteocytes have come to the forefront of skeletal biology and are now recognized as a key cell type that integrates hormonal, mechanical and other signals to control bone mass through regulation of both osteoblast and osteoclast activity. With the surge of recent interest in osteocytes as bone regulatory cells and the discovery that they also function as endocrine regulators of phosphate homeostasis, there has been renewed interest in understanding the structure and function of these unique and relatively inaccessible cells. Osteocytes are embedded within the mineralized bone matrix and are housed within a complex lacunocanalicular system which connects them with the circulation and with other organ systems. This has presented unique challenges for imaging these cells. This review summarizes recent advances in confocal imaging approaches for visualizing osteocytes and their lacunocanalicular networks in both living and fixed bone specimens and discusses how computational approaches can be combined with live and fixed cell imaging techniques to generate quantitative outputs and predictive models. The integration of advanced imaging with computational approaches promises to lead to a more in depth understanding of the structure and function of osteocyte networks and the lacunocanalicular system in the healthy and aging state as well as in pathological conditions in bone.