Osteoblast-osteoclast co-cultures: A systematic review and map of available literature

PLoS One. 2021 Nov 4;16(11):e0257724. doi: 10.1371/journal.pone.0257724. eCollection 2021.

Abstract

Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models is to use in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods, leading to conceptually similar studies with many methodological differences and, as a consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Bone Resorption / drug therapy*
  • Bone Resorption / genetics
  • Bone Resorption / physiopathology
  • Cell Differentiation / drug effects
  • Coculture Techniques*
  • Databases, Factual
  • Drug Discovery / trends
  • Humans
  • Models, Animal
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects
  • RANK Ligand / genetics

Substances

  • RANK Ligand

Grants and funding

S.J.A.R. was supported by ZonMw More Knowledge with Fewer Animals Programme (MKMD), project number 114024141 (https://www.zonmw.nl). S.J.A.R. and S.H. were financially supported by the European Union’s Seventh Framework Programme (FP/2007-2013), Grant Agreement No. 336043 (project REMOTE) (https://erc.europa.eu). B.W.M.d.W., M.A.M.V. and S.H. are financially supported by the research program TTW with project number TTW 016.Vidi.188.021, which is (partly) financed by the Netherlands Organization for Scientific Research (NWO) (https://www.nwo.nl/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.