Identification and functional characterization of hyaluronic acid in degenerative joint diseases

Abstract

Hyaluronic acid (HA), is a long polysaccharide chain that is made of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. In osteoarthritis (OA) and rheumatoid arthritis, the molecular weight and concentration of HA in synovial fluid (SF) are reduced. This might result from abnormal biosynthesis by synovial type B cells and free radical depolymerization of the HA chain. The intra-articular treatment with HA is an accepted therapy for OA. However, the ideal candidate for intra-articular HA has yet to be defined and the exact mechanism of action of HA is unclear. Our study showed that the levels of ROS and acute phase protein profiles were reduced in patients under going HA treatment. HA could increase the cell viability of human chondrocytes under the high oxidative stress conditions also been determined. The primary receptor for HA is CD44, mediating both cell-cell and cell-matrix interactions. We postulate that the biological process initiated by HA-CD44 interaction results in changes in chondrocytes as well as in SF protein profiles. We used the proteomic approaches to investigate the biological functions of HA. There were 31 proteins, functioning in cell rescue, cell defense, cell stress, energy, anaerobic glycolysis, protein fate, cellular organization and cell cycle involved in this regulatory signaling. It suggests that HA involves in the antioxidative activity, anti-inflammation, anti-catabolic effect and cell growth regulation. This study will contribute to our understanding of HA functioning in the progressive degeneration of cartilage and to explore the clinical application of HA for degenerative joint diseases.