Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes

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 tra...

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Main Authors: Yuta Onodera, Takeshi Teramura, Toshiyuki Takehara, Kanji Fukuda
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1016/j.fob.2015.05.007
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author Yuta Onodera
Takeshi Teramura
Toshiyuki Takehara
Kanji Fukuda
author_facet Yuta Onodera
Takeshi Teramura
Toshiyuki Takehara
Kanji Fukuda
author_sort Yuta Onodera
collection DOAJ
description 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.
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spelling doaj.art-6481c50207494948b790650f2534062e2022-12-22T02:57:50ZengWileyFEBS Open Bio2211-54632015-01-015147648410.1016/j.fob.2015.05.007Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytesYuta Onodera0Takeshi Teramura1Toshiyuki Takehara2Kanji Fukuda3Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, JapanInstitute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, JapanInstitute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, JapanInstitute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, JapanOne 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.https://doi.org/10.1016/j.fob.2015.05.007Hyaluronic acidReactive oxygen species (ROS)Nuclear factor-erythroid-2-related factor 2 (Nrf2)Chondrocytes
spellingShingle Yuta Onodera
Takeshi Teramura
Toshiyuki Takehara
Kanji Fukuda
Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
FEBS Open Bio
Hyaluronic acid
Reactive oxygen species (ROS)
Nuclear factor-erythroid-2-related factor 2 (Nrf2)
Chondrocytes
title Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
title_full Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
title_fullStr Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
title_full_unstemmed Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
title_short Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
title_sort hyaluronic acid regulates a key redox control factor nrf2 via phosphorylation of akt in bovine articular chondrocytes
topic Hyaluronic acid
Reactive oxygen species (ROS)
Nuclear factor-erythroid-2-related factor 2 (Nrf2)
Chondrocytes
url https://doi.org/10.1016/j.fob.2015.05.007
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