title: Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes.
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.
authors.affiliation: Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Onodera
authors.affiliation: Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Teramura
authors.affiliation: Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Fukuda
keywords: Chondrocytes; HA, hyaluronic acid; Hyaluronic acid; Nrf2, nuclear factor-erythroid-2-related factor 2; Nuclear factor-erythroid-2-related factor 2 (Nrf2); ROS, reactive oxygen species; Reactive oxygen species (ROS)