RT Journal Article SR Electronic T1 Secondary ossification center induces and protects growth plate structure JF bioRxiv FD Cold Spring Harbor Laboratory SP 571612 DO 10.1101/571612 A1 Meng Xie A1 Pavel Gol’din A1 Anna Nele Herdina A1 Jordi Estefa A1 Ekaterina V Medvedeva A1 Lei Li A1 Phillip T Newton A1 Svetlana Kotova A1 Boris Shavkuta A1 Aditya Saxena A1 Lauren T Shumate A1 Brian Metscher A1 Karl Großschmidt A1 Shigeki Nishimori A1 Anastasia Akovantseva A1 Anna P Usanova A1 Anastasiia D Kurenkova A1 Anoop Kumar A1 Irene Linares Arregui A1 Paul Tafforeau A1 Kaj Fried A1 Mattias Carlström A1 Andras Simon A1 Christian Gasser A1 Henry M Kronenberg A1 Murat Bastepe A1 Kimberly L. Cooper A1 Peter Timashev A1 Sophie Sanchez A1 Igor Adameyko A1 Anders Eriksson A1 Andrei S Chagin YR 2020 UL http://biorxiv.org/content/early/2020/09/01/571612.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.