3R PRINCIPLE; ANIMAL EXPERIMENTS; ANIMAL WELFARE; BONE; IN SILICO MODELS; NON ANIMAL MODELS; PRECLINICAL RESEARCH; SKELETON; Orthopedics and Sports Medicine; Endocrinology, Diabetes and Metabolism
Abstract :
[en] Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last few years. Nevertheless, the overall complexity of bone tissue cross-talk and the systemic and local regulation of bone physiology can often only be addressed in entire vertebrates. Powerful genetic methods such as conditional mutagenesis, lineage tracing, and modeling of the diseases enhanced the understanding of the entire skeletal system. In this review endorsed by the European Calcified Tissue Society (ECTS), a working group of investigators from Europe and the US provides an overview of the strengths and limitations of experimental animal models, including rodents, fish, and large animals, as well the potential and shortcomings of in vitro and in silico technologies in skeletal research. We propose that the proper combination of the right animal model for a specific hypothesis and state-of-the-art in vitro and/or in silico technology is essential to solving remaining important questions in bone research. This is crucial for executing most efficiently the 3R principles to reduce, refine, and replace animal experimentation, for enhancing our knowledge of skeletal biology, and for the treatment of bone diseases that affect a large part of society.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Stein, Merle; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany
Elefteriou, Florent ; Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX, USA ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Busse, Björn; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Interdisciplinary Competence Center for Interface Research (ICCIR), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Fiedler, Imke Ak; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Interdisciplinary Competence Center for Interface Research (ICCIR), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Kwon, Ronald Young; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, WA, USA ; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
Farrell, Eric; Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Ahmad, Mubashir ; Institute of Orthopaedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
Ignatius, Anita ; Institute of Orthopaedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
Grover, Liam; Healthcare Technologies Institute, Institute of Translational Medicine, Birmingham, UK
Geris, Liesbet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique ; Skeletal Biology & Engineering Research Center, KU Leuven, Leuven, Belgium
Tuckermann, Jan ; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany
Language :
English
Title :
Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.
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