Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes

Abstract

The osteocyte is believed to act as the main sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on our bones throughout life. However, the precise mechanical stimuli that bone cells experience in vivo are not yet fully understood. The objective of this study is to use computational methods to predict the loading conditions experienced by osteocytes during normal physiological activities. Confocal imaging of the lacunar -canalicular network was used to develop three-dimensional finite element models of osteocytes, including their cell body, and the surrounding pericellular matrix (PCM) and extracellular matrix (ECM). We investigated the role of the PCM and ECM projections for amplifying mechanical stimulation to the cells. At loading levels, representing vigorous physiological activity (3000 m1), our results provide direct evidence that (i) confocal image-derived models predict 350 -400% greater strain amplification experienced by osteocytes compared with an idealized cell, (ii) the PCM increases the cell volume stimulated more than 3500 m1 by 4 -10% and (iii) ECM projections amplify strain to the cell by approximately 50 -420%. These are the first confocal image-derived computational models to predict osteocyte strain in vivo and provide an insight into the mechanobiology of the osteocyte.

Mechanisms of osteocyte stimulation in osteoporosis

“…By applying computational modelling approaches we predicted that such changes can lead to an increase in osteogenic strain stimulation of osteocytes, both with and without cellular attachments. These results reinforce our previous findings that osteocytes are highly sensitive to changes in canalicular geometry (Verbruggen et al 2012), and suggest that canalicular tortuosity may be a mechanism by which osteocytes may sense osteoporotic changes. However, when compared to the increases in osteogenic strain stimulation observed in our experimental study it was seen that, while tortuosity may contribute, it cannot completely explain the difference in osteoporosis.…”

“…In particular it has been demonstrated that the lacunar-canalicular network in cortical bone in humans with osteoporosis is disorganised, with a more tortuous canalicular anatomy compared to healthy subjects (Knothe Tate et al 2002;Knothe Tate et al 2004). As demonstrated previously through the use of computational models to replicate the osteocyte mechanical environment (Anderson and Knothe Tate 2008;Kamioka et al 2012;Verbruggen et al 2012;Verbruggen et al 2013), osteocyte stimulation is highly sensitive to the surrounding lacunar-canalicular architecture. Therefore, this increase in tortuosity during osteoporosis would likely affect the mechanical stimulation of the osteocyte in vivo, although this effect remains to be elucidated.…”

“…Finite element models, described in detail in a previous study (Verbruggen et al 2012), were employed to investigate the effects of alterations in material properties on the strain stimulation experienced by the osteocyte. Briefly, these models were derived from confocal laser scanning microscopy images of fluorescein isothiocyanate (FITC)-stained osteocyte lacunae, and thereby closely represent their geometry in vivo (see Figure 1).…”

“…The lacuna was modelled as an ellipsoid of minor and major axes 9 and 15 mm, respectively, while canaliculi were included as cylindrical channels of diameter 0.6 mm (Verbruggen et al 2012). The osteocyte was also modelled as an ellipsoid with minor and major axes of 7.5 and 13.5 mm, respectively, surrounded by a PCM of thickness 0.75 mm (McNamara et al 2009;You et al 2004).…”

Fluid flow in the osteocyte mechanical environment: a fluid–structure interaction approach

“…In all previous computational models bone cells and tissue were modelled using either The objective of this research is to use computational methods to predict the mechanical Models of an idealised osteocyte and an idealised osteocyte with ECM projections were 23 generated to compare with the representative geometries (Verbruggen et al 2012), similar to the methods described above. The four representative geometries and the idealised geometry 1 are shown in Fig.…”