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Secondary ossification center induces and protects growth plate structure
(Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden)
(Department of Evolutionary Morphology, Schmalhausen Institute of Zoology of NAS of Ukraine, Ukraine)
(Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
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(English)In: eLIFE, E-ISSN 2050-084XArticle in journal (Refereed) Submitted
Abstract [en]

Growth plate and articular cartilage constitute a single anatomical entity, but later separate into two distinct structures by the formation of secondary ossification center (SOC). The reason for such spatial separation remains unknown. Here, we demonstrate that evolutionarily SOC first appears in amniotes. Mathematical modelling reveals that SOC reduces mechanical stress within the growth plate. Analysis of mammals with specialized extremities reveals that SOC size correlates with the extent of mechanical demands. Ex and in vivo experiments demonstrate that SOC allows epiphyseal chondrocytes to withstand a several-fold higher load before activation of the YAP-p73 signalling pathway and caspase-dependent apoptosis, with hypertrophic chondrocytes being the most load-sensitive cells. Atomic force microscopy shows  that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC is evolved to protect epiphyseal chondrocytes, especially the hypertrophic chondrocytes, from the high mechanical stress encountered in the terrestrial environment.

National Category
Evolutionary Biology
Identifiers
URN: urn:nbn:se:uu:diva-405966OAI: oai:DiVA.org:uu-405966DiVA, id: diva2:1411109
Available from: 2020-03-03 Created: 2020-03-03 Last updated: 2020-03-03
In thesis
1. Long bone growth and evolution revealed by three-dimensional imaging
Open this publication in new window or tab >>Long bone growth and evolution revealed by three-dimensional imaging
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Propagation phase-contrast synchrotron radiation microtomography is a non-destructive method used for studying histology in three dimensions (3D). Using it, the 3D organization of the diaphyseal cortical vascularization in the humerus of two seymouriamorphs was analyzed in this thesis. Their vascularization suggests a combination of active growth and a long pre-reproductive period, an intermediate condition between that of Devonian tetrapods and early amniotes, reflecting a gradual change in evolution. The focus of the thesis then shifts to the metaphysis of long bones. The latter possesses complex 3D structures difficult to capture in 2D images. Observations in extant tetrapods have shown that hematopoiesis in long-bones requires the presence of tubular marrow processes opening onto an open medullary cavity with a centralized vascular system. A network of tubular marrow processes was found in connection with interconnected small cavities in the metaphyses of seymouriamorphs which may have acted as open spaces containing a centralized vascular mesh. Based on this interpretation, the long-bone marrow cavity of the Permian stem-amniotes studied here could have been the oldest evidence of possible hematopoiesis among tetrapods. As a third focus, both computer simulations (Finite Element Analysis) and empirical experiments were conducted to investigate the role of Secondary Ossification Centers (SOCs) within the epiphyses of mammals. The results indicate that the presence of a SOC protects the growth plate from mechanical stresses, allowing the cells there to withstand six times more stress. Finally, the 3D microanatomy of the metaphyses and epiphyses in the humeri of monotreme, marsupial and placental extant mammals were investigated at different developmental stages. The data were used to produce a nomenclature based on the degree of epiphyseal ossification encompassing the entire development of all the condyles within a single epiphysis. This nomenclature was used to describe the epiphyseal development in a large group of mammals and highlight differences in ossification timing between groups. These results offer a unique glimpse into the development and evolution of long-bones. They highlight the value of visualizing long-bone microstructure in both 2D and 3D, and the need to develop new nomenclatures that reflect the 3D nature of the data.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 52
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1910
Keywords
3D histology, hematopoiesis, humerus, tetrapods
National Category
Developmental Biology Evolutionary Biology
Research subject
Biology
Identifiers
urn:nbn:se:uu:diva-405974 (URN)978-91-513-0885-2 (ISBN)
Public defence
2020-04-20, Lindahlsalen, EBC, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2020-03-31 Created: 2020-03-03 Last updated: 2020-03-31

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