The Small World of Osteocytes: Connectomics of the Lacuno-Canalicular Network in Bone

TL;DR

This study quantitatively analyzes the osteocyte lacuno-canalicular network in bone, revealing universal self-organization principles across species and bone types using complex network theory.

Contribution

It introduces a novel quantitative approach to characterize the cellular network in bone and compares network organization across different species and bone types.

Findings

Sheep bone networks are less connected but more efficient than mouse networks.

Topological properties are similar across species and bone types despite tissue differences.

Universal self-organization mechanisms govern osteocyte network formation.

Abstract

Osteocytes and their cell processes reside in a large, interconnected network of voids pervading the mineralized bone matrix of most vertebrates. This osteocyte lacuno-canalicular network (OLCN) is believed to play important roles in mechanosensing, mineral homeostasis, and for the mechanical properties of bone. While the extracellular matrix structure of bone is extensively studied on ultrastructural and macroscopic scales, there is a lack of quantitative knowledge on how the cellular network is organized. Using a recently introduced imaging and quantification approach, we analyze the OLCN in different bone types from mouse and sheep that exhibit different degrees of structural organization not only of the cell network but also of the fibrous matrix deposited by the cells. We define a number of robust, quantitative measures that are derived from the theory of complex networks. These measures enable us to gain insights into how efficient the network is organized with regard to intercellular transport and communication. Our analysis shows that the cell network in regularly organized, slow-growing bone tissue from sheep is less connected, but more efficiently organized compared to irregular and fast-growing bone tissue from mice. On the level of statistical topological properties (edges per node, edge length and degree distribution), both network types are indistinguishable, highlighting that despite pronounced differences at the tissue level, the topological architecture of the osteocyte canalicular network at the subcellular level may be independent of species and bone type. Our results suggest a universal mechanism underlying the self-organization of individual cells into a large, interconnected network during bone formation and mineralization.