Abstract
One important pharmacological function of hyaluronic acid (HA) in chondrocytes is reduction of cellular superoxide generation and accumulation. Here we demonstrated a relationship between HA supplementation and accumulation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), which is a master transcription factor in cellular redox reactions, in cultured chondrocytes derived from bovine joint cartilage. In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. In HA-treated chondrocytes, Akt was phosphorylated, and inhibition of Akt activity or suppression of HA receptors CD44 and/or RHAMM with siRNAs prevented HA-mediated Nrf2 accumulation. Furthermore, Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. These results show that HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. Our study suggests a new mechanism for extracellular matrix (ECM)-mediated redox systems in chondrocytes.
Highlights
Articular cartilage is a unique tissue in which a single resident cell type, the chondrocyte exists in a specific environment that is avascular, aneural, alymphatic, but consist of abundant extracellular matrix (ECM) with a tissue specific pattern of proteoglycans (PGs), glycoproteins, collagens and hyaluronic acid (HA) [1,2,3,4]
These results indicate that H2O2 induced reactive oxygen species (ROS) elevation is detrimental to matrix maintenance, and HA supplementation can function as an antioxidative factor to assuage the catabolic changes at gene expressions level in the cultured chondrocytes
This study examined the hypothesis that the protective effects of HA in chondrocytes may be related to enhancement of the Nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidation potential
Summary
Articular cartilage is a unique tissue in which a single resident cell type, the chondrocyte exists in a specific environment that is avascular, aneural, alymphatic, but consist of abundant extracellular matrix (ECM) with a tissue specific pattern of proteoglycans (PGs), glycoproteins, collagens and hyaluronic acid (HA) [1,2,3,4]. This macromolecular assembly directly relates to maintenance of the chondrocyte phenotype [5,6,7].
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