UNDERSTANDING THE ROLE OF SULFUR IN CARTILAGE DEVELOPMENT: HOW STRUCTURAL PROTEOGLYCANS ARE IMPLICATED IN CARTILAGE MATURATION

Abstract

Cartilage is a vital tissue of the adult skeleton, which also serves as a transitional structure during early skeletal development. Sulfation of proteoglycans, especially chondroitin sulfate proteoglycans (CSPGs), lends unique mechanical properties to this tissue; but how CSPG sulfation relates to cartilage growth and development remains an open area of study. Though the basic biochemistry of addition and removal of sulfate groups from sulfated proteoglycans has been well studied, we reveal for the first time in the chicken the spatial distribution of sulfur throughout the cartilage template of a developing endochondral bone (the humerus) to show that changes in sulfation pattern are related to cartilage maturation. New techniques such as chemically specific X-ray fluorescence (XRF) imaging combined with immunohistochemistry allow the testing of the hypothesis that sulfate ester levels are correlated with the underlying cartilage maturation state. Our findings indicate that there is a significant decrease in sulfate ester levels in mature cartilage when compared with immature cartilage in the chicken. No significant decrease in PGs occurred at this time point in mature cartilage according to infrared imaging, suggesting an under-sulfated CSPG molecule in mature cartilage, and an unknown mechanism responsible for this shift in lowered sulfation levels. Decreasing sulfate esters in mature cartilage are now shown to be features of skeletal development for the chicken in addition to zebrafish.