Secondary ossification center induces and protects growth plate structure

• DOI: 10.7554/elife.55212
• Publication Date: 2020-10-16T12:00:32Z
• Authors: Meng Xie; Pavel Gol'din; Anna Nele Herdina; Jordi Estefa; Ekaterina V Medve...; Lei Li; Phillip T Newton; Svetlana Kotova; Boris Shavkuta; Aditya Saxena; Lauren T Shumate; Brian D Metscher; Karl Großschmidt; Shigeki Nishimori; Anastasia Akovant...; Anna P Usanova; Anastasiia D Kure...; Anoop Kumar; Irene Linares Arr...; Paul Tafforeau; Kaj Fried; Mattias Carlström; András Simon; Christian Gasser; Henry M Kronenberg; Murat Bastepe; Kimberly L Cooper; Peter Timashev; Sophie Sanchez; Igor Adameyko; Anders Eriksson; Andrei S Chagin
• Keywords: 0301 basic medicine; LIMB POSTURE; WING MORPHOLOGY; secondary ossification; QH301-705.5; Science; chondrocytes; bat; 106054 Zoology; LONG BONES; General Biochemistry, Genetics and Molecular Biology; Evolutionsbiologi; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Chondrocytes; Osteogenesis; growth plate; Animals; Growth Plate; Biology (General); Cell Proliferation; Evolutionary Biology; 0303 health sciences; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; General Immunology and Microbiology; General Neuroscience; CHONDROCYTES; PRIMITIVE FORM; Q; R; BAT; Cell Differentiation; General Medicine; whale; EVOLUTION; Biomechanical Phenomena; Rats; Mice, Inbred C57BL; 106054 Zoologie; MECHANICS; Medicine; Stress, Mechanical; SKELETAL DEVELOPMENT; jerboa; TERRESTRIAL LOCOMOTION; Developmental Biology

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 the ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modeling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed the 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.