High-resolution image-based simulation reveals membrane strain concentration on osteocyte processes caused by tethering elements

Yuka Yokoyama,Hiroshi Kamioka,Taiji Adachi,Yoshitaka Kameo

doi:10.1007/s10237-021-01511-y

Yuka Yokoyama, Hiroshi Kamioka + Show 2 more

Open Access

https://doi.org/10.1007/s10237-021-01511-y

Copy DOI

Abstract

Osteocytes are vital for regulating bone remodeling by sensing the flow-induced mechanical stimuli applied to their cell processes. In this mechanosensing mechanism, tethering elements (TEs) connecting the osteocyte process with the canalicular wall potentially amplify the strain on the osteocyte processes. The ultrastructure of the osteocyte processes and canaliculi can be visualized at a nanometer scale using high-resolution imaging via ultra-high voltage electron microscopy (UHVEM). Moreover, the irregular shapes of the osteocyte processes and the canaliculi, including the TEs in the canalicular space, should considerably influence the mechanical stimuli applied to the osteocytes. This study aims to characterize the roles of the ultrastructure of osteocyte processes and canaliculi in the mechanism of osteocyte mechanosensing. Thus, we constructed a high-resolution image-based model of an osteocyte process and a canaliculus using UHVEM tomography and investigated the distribution and magnitude of flow-induced local strain on the osteocyte process by performing fluid–structure interaction simulation. The analysis results reveal that local strain concentration in the osteocyte process was induced by a small number of TEs with high tension, which were inclined depending on the irregular shapes of osteocyte processes and canaliculi. Therefore, this study could provide meaningful insights into the effect of ultrastructure of osteocyte processes and canaliculi on the osteocyte mechanosensing mechanism.

Highlights

Osteocytes are the most abundant cells present inside the bone matrix and are vital for bone remodeling as they regulate osteoclastic bone resorption and osteoblastic boneIn the mechanosensing of osteocytes, local strain on the cell process membrane is considered a representative indicator of mechanical stimuli as it can activate gating of mechanosensitive ion channels such as Piezo1 (McMahon et al 2008; Li et al 2019; Diem et al 2020; Sasaki et al 2020; Zhou et al 2020)
Upon focusing on individual tethering elements (TEs), the TE that was aligned upstream in the + z flow (θ > π∕2 ) generated a strain concentration on the osteocyte process under the + z flow condition (Fig. 4c), whereas the TE inclined upstream to the − z flow ( θ < π∕2 ) generated a strain concentration under the − z flow condition (Fig. 4d). These results indicate that the relative angle of the TEs to the flow direction, which can be determined based on the irregular shapes of osteocyte processes and canaliculi, is a crucial factor in producing a strain concentration in the osteocyte process
The simulation results revealed that specific TEs with high tension, which depend on the irregular shapes of osteocyte processes and canaliculi, can generate a local strain concentration in the osteocyte process

Summary

Introduction

Osteocytes are the most abundant cells present inside the bone matrix and are vital for bone remodeling as they regulate osteoclastic bone resorption and osteoblastic boneIn the mechanosensing of osteocytes, local strain on the cell process membrane is considered a representative indicator of mechanical stimuli as it can activate gating of mechanosensitive ion channels such as Piezo (McMahon et al 2008; Li et al 2019; Diem et al 2020; Sasaki et al 2020; Zhou et al 2020). The interstitial fluid flow generated by external forces in the canalicular space is considered a principal factor in strain amplification (Weinbaum et al 1994; Zeng et al 1994; Scheiner et al 2016). Tethering elements (TEs) connecting the osteocyte process to the canalicular wall, which are regarded as the core protein of perlecan, are supposed to provide drag force to the cell processes via interstitial fluid flow (You et al 2001; Han et al 2004; Wang et al 2007, 2014)

Objectives

Methods

Results

Conclusion