Do chondroitin sulfates with different structures have different activities on chondrocytes and macrophages?

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da Cunha, Andre L. [UNIFESP]
Aguiar, Jair A. K. [UNIFESP]
Correa da Silva, Flavio S.
Michelacci, Yara M. [UNIFESP]
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The aim of the present study was to investigate the activities of natural chondroitin sulfates (CS) with different structures on cultured chondrocytes and macrophages. CS were isolated from cartilages of bovine trachea (BT), porcine trachea (PT), chicken sternum (Ch) and skate (Sk). The preparations were 90-98% pure, with similar to 1% proteins, nucleic acids and keratan sulfate contaminants. Structural analysis of these CS and of commercial chondroitin 4- and 6-sulfate (C4S, C6S) have shown that most of their disaccharides are monosulfated, with varying proportions of 4- and 6-sulfation, and 2-7% non-sulfated disaccharides. Sk-CS and C6S contained detectable amounts of disulfated disaccharides. All the CS were polydisperse, with modal molecular weights of 26-135 kDa. These CS had anti-inflammatory activities on both chondrocytes and macrophages, but with different efficiencies. On horse and human chondrocytes, they reduced the IL-1 beta-induced liberation of NO and PGE(2), and on RAW 264.7 immortalized macrophage-like cell line, C4S, C6S, Ch and Sk-CS decreased the LPS-induced liberation of TNF-alpha, but did not affect IL-6. In contrast, on bone marrow derived macrophages, C4S, C6S, BT and PT-CS reduced the LPS-induced liberation of TNF-alpha, IL-6, IL-1 beta and NO, indicating that the RAW response to CS was different from that of primary macrophages. (C) 2017 Elsevier B.V. All rights reserved.
International Journal Of Biological Macromolecules. Amsterdam, v. 103, p. 1019-1031, 2017.