期刊
FEBS OPEN BIO
卷 5, 期 -, 页码 476-484出版社
WILEY
DOI: 10.1016/j.fob.2015.05.007
关键词
Hyaluronic acid; Reactive oxygen species (ROS); Nuclear factor-erythroid-2-related factor 2 (Nrf2); Chondrocytes
资金
- Japan Society for the Promotion of Science (JSPS) [24791572, 25462388]
- Grants-in-Aid for Scientific Research [24791572, 25462388] Funding Source: KAKEN
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. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. This is an open access article under the CC BY license.
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