New and Old Osteocytic Cell Lines and 3D Models

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OSTEOCYTES (J DELGADO-CALLE AND J KLEIN-NULEND, SECTION EDITORS)

New and Old Osteocytic Cell Lines and 3D Models Paola Divieti Pajevic 1

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Purpose of Review The aim of this review was to compile a list of tools currently available to study bone cells and in particular osteocytes. As the interest (and importance) in osteocyte biology has greatly expanded over the past decade, new tools and techniques have become available to study these elusive cells, Recent Findings Osteocytes are the main orchestrators of bone remodeling. They control both osteoblasts and osteoclast activities via cell-to cell communication or through secreted factors. Osteocytes are also the mechanosensors of the bone and they orchestrate skeletal adaptation to loads. Recent discoveries have greatly expanded our knowledge and understanding of these cells and new models are now available to further uncover the functions of osteocytes. Summary Novel osteocytic cell lines, primary cultures, and 3D scaffolds are now available to investigators to further unravel the functions and roles of these cells. Keywords Osteocytes . Scaffolds . 3D culture

Introduction The last decade has seen an expansion in the tools and models available to study skeletal processes and the establishment of new cell lines has proven fundamental in the discovery of novel therapeutics for skeletal diseases. Historically, osteocytes posed a technical challenge to biologists due to their location within the mineralized matrix and the associated difficulties in isolate and characterize these cells. The extensive cell-to-cell communication and the architecture of the lacuna-canalicular network suggested two possible functions for these cells: to ensure communication between osteocytes deep within the matrix with the surrounding tissues and to provide an extensive surface for mineral exchanges [1]. It was postulated that osteocytes could mobilize calcium through a mechanism called “osteocytic osteolysis” and that this process was regulated by calciotropic hormones (parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D3) [2, 3]. This article is part of the Topical Collection on Osteocytes * Paola Divieti Pajevic [email protected] 1

Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, 700 Albany Street, W201E, Boston, MA 02118, USA

Histological observations that in various physiological and pathological states the size of the osteocytic lacunae was increased supported this hypothesis. The idea of “osteocytic osteolysis” was quickly abandoned when isolated chick osteocytes failed to reabsorb bone is a classical osteoclast pitforming assay. Recent studies, however, have demonstrated that osteocyte-mediated calcium mobilization and remodeling of the perilacunar spaces are important for lactation [4, 5]. Nevertheless, the exact mechanism by which osteocytes control calcium homeostasis remains elusive. In the late 1980s, Harold Frost initiated a series of investigations wh