Non-traumatic rotator cuff tears (RCTs) are a frequent and potentially disabling injury. There is growing evidence that hyaluronic acid is effective for pain relief and to counteract inflammation in RCTs, however, its effective role in tendinopathies remains poorly studied. The present study aims to disclose a possible molecular mechanism underlying the cytoprotective effects of four different hyaluronic acid preparations (Artrosulfur HA®, Synolis-VA®, Hyalgan® and Hyalubrix®) under H2O2-induced oxidative stress. Expression-levels of Lactate dehydrogenase (LDH) released were quantified in cell supernatants, CD44 expression levels were analysed by fluorescence microscopy, the mitochondrial membrane depolarization (TMRE assay) was measured by flow cytometry and the role of the transcription factor Nrf2 was investigated as a potential therapeutic target for RCT treatment. The modulation of extracellular matrix- (ECM) related protein expression (Integrin β1, Pro-collagen 1A2 and Collagen 1A1) and autophagy occurrence (Erk 1/2 and phosphoErk 1/2 and LC3B), were all investigated by Western Blot. Results demonstrate that Artrosulfur HA, Hyalubrix and Hyalgan improve cell escape from H2O2-induced oxidative stress, decreasing cytotoxicity, reducing Nrf2 expression and enhancing catalase recovery. The present study lays the grounds for further investigations insight novel pharmaceutical strategies targeting key effectors involved in the molecular cascade triggered by hyaluronic acid

Nrf2-mediated cytoprotective effect of four different hyaluronic acids by molecular weight in human tenocytes

Gallorini M;Amelia Cataldi;
2020

Abstract

Non-traumatic rotator cuff tears (RCTs) are a frequent and potentially disabling injury. There is growing evidence that hyaluronic acid is effective for pain relief and to counteract inflammation in RCTs, however, its effective role in tendinopathies remains poorly studied. The present study aims to disclose a possible molecular mechanism underlying the cytoprotective effects of four different hyaluronic acid preparations (Artrosulfur HA®, Synolis-VA®, Hyalgan® and Hyalubrix®) under H2O2-induced oxidative stress. Expression-levels of Lactate dehydrogenase (LDH) released were quantified in cell supernatants, CD44 expression levels were analysed by fluorescence microscopy, the mitochondrial membrane depolarization (TMRE assay) was measured by flow cytometry and the role of the transcription factor Nrf2 was investigated as a potential therapeutic target for RCT treatment. The modulation of extracellular matrix- (ECM) related protein expression (Integrin β1, Pro-collagen 1A2 and Collagen 1A1) and autophagy occurrence (Erk 1/2 and phosphoErk 1/2 and LC3B), were all investigated by Western Blot. Results demonstrate that Artrosulfur HA, Hyalubrix and Hyalgan improve cell escape from H2O2-induced oxidative stress, decreasing cytotoxicity, reducing Nrf2 expression and enhancing catalase recovery. The present study lays the grounds for further investigations insight novel pharmaceutical strategies targeting key effectors involved in the molecular cascade triggered by hyaluronic acid
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/708457
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