Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones

Much of the vertebrate skeleton develops from cartilage templates that are progressively remodeled into bone. Lineage tracing studies in mouse suggest that chondrocytes within these templates persist and become osteoblasts, yet the underlying mechanisms of this process and whether chondrocytes can g...

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Bibliographic Details
Published in:eLife 2019-02, Vol.8
Main Authors: Giovannone, Dion, Paul, Sandeep, Schindler, Simone, Arata, Claire, Farmer, D'Juan T, Patel, Punam, Smeeton, Joanna, Crump, J Gage
Format: Article
Language:English
Subjects:
adipocyte
Adipocytes
Adipocytes - cytology
Adipose tissue
Animal genetic engineering
Animals
Bone Marrow Cells - cytology
Bones
Cartilage
Cartilage - growth & development
Cell cycle
Cell Differentiation - genetics
chondrocyte
Chondrocytes
Chondrocytes - cytology
Collagen Type II - genetics
Danio rerio
Derivatives (Financial instruments)
Developmental Biology
Dwarfism
endochondral bone
Fate
Fluorescence
Gelatinase B
Gene Expression Regulation, Developmental
Genetic engineering
Genetically modified organisms
Growth plate
Growth Plate - growth & development
Leptin
Mammals
Matrix metalloproteinase
Mesenchyme
Metalloproteinase
Mmp9
osteoblast
Osteoblasts
Osteoblasts - cytology
skeletal stem cell
Skeleton
Sox10 protein
SOXE Transcription Factors - genetics
Stem cells
Stem Cells and Regenerative Medicine
Time
Vascularization
Zebrafish
Zebrafish - genetics
Zebrafish - growth & development
Zebrafish Proteins - genetics
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Description
Summary:Much of the vertebrate skeleton develops from cartilage templates that are progressively remodeled into bone. Lineage tracing studies in mouse suggest that chondrocytes within these templates persist and become osteoblasts, yet the underlying mechanisms of this process and whether chondrocytes can generate other derivatives remain unclear. We find that zebrafish cartilages undergo extensive remodeling and vascularization during juvenile stages to generate fat-filled bones. Growth plate chondrocytes marked by and contribute to osteoblasts, marrow adipocytes, and mesenchymal cells within adult bones. At the edge of the hypertrophic zone, chondrocytes re-enter the cell cycle and express ( ), suggesting conversion into progenitors. Further, mutation of ( ) results in delayed growth plate remodeling and fewer marrow adipocytes. Our data support Mmp9-dependent growth plate remodeling and conversion of chondrocytes into osteoblasts and marrow adipocytes as conserved features of bony vertebrates.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.42736