Secondary ossification center induces and protects growth plate structure
- Karolinska Institutet, Sweden
- Schmalhausen Institute of Zoology of NAS of Ukraine, Ukraine
- Uppsala University, Evolutionary Biology Centre, Sweden
- Sechenov University, Russian Federation
- University of California San Diego, United States
- Massachusetts General Hospital and Harvard Medical School, United States
- University of Vienna, Austria
- Medical University of Vienna, Austria
- KTH Royal Institute of Technology, Sweden
- European Synchrotron Radiation Facility, France
- Univeristy of California, San Diego, United States
Abstract
Growth plate and articular cartilage constitute a single anatomical entity early in development, but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modelling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
EMBO
- Meng Xie
- Igor Adameyko
Svenska Forskningsrådet Formas
- Sophie Sanchez
- Igor Adameyko
- Andrei S Chagin
Russian Science Foundation
- Peter Timashev
Stiftelsen Frimurare Barnhuset i Stockholm
- Meng Xie
- Phillip T Newton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: all animal experiments were pre-approved by the Ethical Committee on Animal Experiments (N5/16, N187/15, 9091-2018, Stockholm North Committee/ Norra Djurförsöksetiska Nämnden), the Institutional Animal Care and Use Committee of the Massachusetts General Hospital (Protocols #: 2005N000094 and 2004N000176) or the University of California San Diego (D16-00020) and conducted in accordance with the provisions and guidelines for animal experimentation formulated by the Swedish Animal Agency. Animal experiments involving limb unloading, AFM and nanoindentation were pre-approved by the Ethics Committee of the Sechenov First State Moscow Medical University (No. 07-17 from 13.09.2017, Moscow, Russia).
Copyright
© 2020, Xie et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Secondary ossification center induces and protects growth plate structure
eLife 9:e55212.
https://doi.org/10.7554/eLife.55212
