Title: High-resolution 3D imaging of osteocytes and computational modelling in mechanobiology: insights on bone development, ageing, health and disease

Authors: PM Goggin, KC Zygalakis, ROC Oreffo, P Schneider

Address: Faculty of Engineering and the Environment, University of Southampton, Southampton, SO17 1BJ, UK

E-mail: p.schneider at soton.ac.uk

Key Words: Osteocyte, 3D imaging, microscopy, biomechanics, lacuno-canalicular network, mechanobiology, mechanosensation, mechanotransduction, osteoporosis

Publication date: May 22nd 2016

Abstract: Osteocytes are involved in mechanosensation and mechanotransduction in bone and hence, are key to bone adaptation in response to development, ageing and disease. Thus, detailed knowledge of the three-dimensional (3D) structure of the osteocyte network (ON) and the surrounding lacuno-canalicular network (LCN) is essential. Enhanced understanding of the ON&LCN will contribute to a better understanding of bone mechanics on cellular and sub-cellular scales, for instance through improved computational models of bone mechanotransduction. Until now, the location of the ON within the hard bone matrix and the sub-µm dimensions of the ON&LCN have posed significant challenges for 3D imaging. This review identifies relevant microstructural phenotypes of the ON&LCN in health and disease and summarises how light microscopy, electron microscopy and X-ray imaging techniques have been used in studies of osteocyte anatomy, pathology and mechanobiology to date. In this review, we assess the requirements for ON&LCN imaging and examine the state of the art in the fields of imaging and computational modelling as well as recent advances in high-resolution 3D imaging. Suggestions for future investigations using volume electron microscopy are indicated and we present new data on the ON&LCN using serial block-face scanning electron microscopy. A correlative approach using these high-resolution 3D imaging techniques in conjunction with in silico modelling in bone mechanobiology will increase understanding of osteocyte function and, ultimately, lead to improved pathways for diagnosis and treatment of bone diseases such as osteoporosis.

Article download: Pages 264-295 (PDF file)
DOI: 10.22203/eCM.v031a18

Supplementary video file (avi): SuppVid1
First serial block-face scanning electron microscopy (SBF SEM) images for bone tissue. Mouse bone, showing individual slices from the image stack and part of an osteocyte in 3D reconstruction.