From the Clinical Problem to the Basic Research—Co-Culture Models of Osteoblasts and Osteoclasts

Abstract

Bone tissue undergoes constant remodeling and healing when fracture happens, in order to ensure its structural integrity. In order to better understand open biological and clinical questions linked to various bone diseases, bone cell co-culture technology is believed to shed some light into the dark. Osteoblasts/osteocytes and osteoclasts dominate the metabolism of bone by a multitude of connections. Therefore, it is widely accepted that a constant improvement of co-culture models with both cell types cultured on a 3D scaffold, is aimed to mimic an in vivo environment as closely as possible. Although in recent years a considerable knowledge of bone co-culture models has been accumulated, there are still many open questions. We here try to summarize the actual knowledge and address open questions.

Melatonin up‐regulates bone marrow mesenchymal stem cells osteogenic action but suppresses their mediated osteoclastogenesis via MT2‐inactivated NF‐κB pathway

“…Since cells can communicate with each other via direct cell‐to‐cell contact or by the secretion of paracrine factor, we imitated these two communication modes and demonstrated that the paracrine secretion model of cytokines (such as RANKL) was responsible for osteoblastic and osteoclastic signal exchange (Figure b). In a direct‐contact model, the existence of cell‐to‐cell contact, such as EphrinB2‐EphB2/B4 and gap junctions between osteoclasts and osteoblasts, may impair RANKL/RANK signalling and lead to the indifference in osteoclastogenesis (Zhu et al, ). Inconsistent with our results, Maria et al believed that melatonin (50 nM) inhibited osteoclastogenesis only through direct cell contact in osteogenic induction condition (Maria et al, ).…”

Bone quality assessment of osteogenic cell cultures by Raman microscopy

“…Although the current study and prior work have primarily focused on evaluating the mineralization capacity specific to Sca‐1 − cells under osteogenic differentiation conditions, studies into how this in vitro osteogenic model compares with other established osteoblast cell lines or primary cell cultures have yet to be performed . Notwithstanding, the immortalized preosteoblast MC3T3‐E1 cell line has also been shown to express the stem cell marker, Sca‐1, which is not unexpected given that this cell line is also derived from newborn mouse calvaria .…”

Strategy for achieving standardized bone models

“…The most minimal in vitro models of bone remodeling fundamentally require the coculture of osteoblasts and osteoclasts (Owen & Reilly, ). Existing coculture models combining osteoblasts, osteoclasts and sometimes osteocytes, predominantly in conventional 2D (138) or static 3D (e.g., gels; Vazquez et al, ), have provided valuable data on osteoblast‐osteoclast interactions and emphasized the role of osteocytes as sensors and orchestrators of the function of both osteoblasts and osteoclasts (Bouet, Cruel, et al, ; Florencio‐Silva et al, ; Owen & Reilly, ; Zhu et al, ).…”

“…The next challenge is the large-scale implementation of standardized 3D perfused systems, leading to operative platforms for fundamental research or clinical and biomedical applications (Junaid, Mashaghi, Hankemeier, & Vulto, 2017;Pirosa, Gottardi, Alexander, & Tuan, 2018;Tandon, Marolt, Cimetta, & Vunjak-Novakovic, 2013 (Kieninger et al, 2018;Zhang et al, 2017). Live-monitoring of specific cell activity markers would provide unique insights into cellular interactions within a dynamic mechanical and chemical environment (Kieninger et al, 2018), such as osteoblast, osteocyte, osteoclast, or adipocyte markers (e.g., alkaline phosphatase, osteocalcin, sclerostin, Trap5b, adiponectin, and FABP4; Daniele et al, 2018;Han, Ju, & Geng, 2018;Wedrychowicz, Sztefko, & Starzyk, 2018;Zhu et al, 2018).…”