BIOLOGICAL EFFECTS OF OLIGOSACCHARIDE CHONDROITIN SULFATE C ON HUMAN ARTICULAR CHONDROCYTES

Abstract

Chondroitin sulfate C (CSC) is an important extracellular matrix (ECM) component of native cartilage tissue. Since ECM is considered to play an important role in guiding proper cellular functions, such as proliferation, differentiation, migration, synthesis or degradation of ECM, in specific tissues, we would like to elucidate the effects of CSC on chondrocytes are cultured on type-II collagen (COL II) scaffolds in this study. In particular, we want to investigate if the oligosaccharides of CSC (O-CSC) have much stronger effects on the chondrocytes. In this in vitro study, human articular chondrocytes were cultured on porous scaffolds made of COL II, cross-linked by genipin. Media containing different molecular weights of CSC were used to cultivate the cells. The results were examined mainly from the gene expression profiles of the cultured cells. The expression levels of several genes were examined by real-time PCR. These included genes of COL II, aggrecan, SRY-related high mobility group-box gene 9 (SOX9) and cartilage oligo matrix protein (COMP), alkaine phosphtase (ALP), a disintegrin and metalloproteinases with thrombospondin motifs 4 (ADAMTS-4), a disintegrin and metalloproteinases with thrombospondin motifs 5 (ADAMTS-5), matrix metalloproteinases 3 (MMP-3) and tissue inhibitors of metalloproteinases 3 (TIMP-3). The results suggested that O-CSC is more potent in upregulating genes that promote chondrogenesis and downregulating genes that degrade cartilage ECM. The results suggest low-molecular-weight glycosaminoglycans may have therapeutic values in osteoarthritis treatment and may lead to further understanding of the basic mechanism of the interactions between the chondrocytes and their ECM.