PUBLICATION

Chemical Biology in the Embryo: In Situ Imaging of Sulfur Biochemistry in Normal and Proteoglycan-Deficient Cartilage Matrix

Authors

Hackett, M.J., George, G.N., Pickering, I.J., Eames, B.F.

ID

ZDB-PUB-160318-2

Date

2016

Source

Biochemistry 55(17): 2441-51 (Journal)

Registered Authors

Eames, Brian F.

Keywords

none

MeSH Terms

Extracellular Matrix/metabolism*
Zebrafish/embryology*
Embryo, Nonmammalian/diagnostic imaging*
Embryo, Nonmammalian/metabolism
Spectroscopy, Fourier Transform Infrared
Cell Differentiation
Sulfur/metabolism*
Proteoglycans/deficiency*
Animals
Cartilage, Articular/metabolism*

PubMed

26985789 Full text @ Biochemistry

Abstract

Proteoglycans are heavily glycosylated proteins that play major structural and biological roles in many tissues. Proteoglycans are abundant in cartilage extracellular matrix; their loss is a main feature of the joint disease osteoarthritis. Proteoglycan function is regulated by sulfation - sulfate ester formation with specific sugar residues. Visualization of sulfation within cartilage matrix would yield vital insights into its biological roles. We present synchrotron-based X-ray fluorescence imaging of developing zebrafish cartilage, providing the first in situ maps of sulfate ester distribution. Both sulfur and sulfate esters decrease as cartilage develops through late phase differentiation (maturation or hypertrophy) suggesting a functional link between cartilage matrix sulfur content and chondrocyte differentiation. Genetic experiments confirm that sulfate ester levels were due to cartilage proteoglycans and support the hypothesis that sulfate ester levels regulate chondrocyte differentiation. Surprisingly, in the PG synthesis mutant, total sulfur was not significantly reduced, suggesting sulfur distributes in an alternative chemical form during lowered cartilage proteoglycan production. Fourier transform infrared imaging indicated increased protein in the mutant fish, suggesting that this alternative sulfur form might be accounted for by increased protein synthesis in the mutant fish, as part of a compensatory mechanism.

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