In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress
Abstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Spr...
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BMC
2021-06-01
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Series: | BMC Musculoskeletal Disorders |
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Online Access: | https://doi.org/10.1186/s12891-021-04398-z |
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author | Shintaro Mukohara Yutaka Mifune Atsuyuki Inui Hanako Nishimoto Takashi Kurosawa Kohei Yamaura Tomoya Yoshikawa Ryosuke Kuroda |
author_facet | Shintaro Mukohara Yutaka Mifune Atsuyuki Inui Hanako Nishimoto Takashi Kurosawa Kohei Yamaura Tomoya Yoshikawa Ryosuke Kuroda |
author_sort | Shintaro Mukohara |
collection | DOAJ |
description | Abstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy. |
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language | English |
last_indexed | 2024-12-18T01:32:49Z |
publishDate | 2021-06-01 |
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spelling | doaj.art-aa7226bdac974422a2261d2bf0338be12022-12-21T21:25:32ZengBMCBMC Musculoskeletal Disorders1471-24742021-06-0122111110.1186/s12891-021-04398-zIn vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stressShintaro Mukohara0Yutaka Mifune1Atsuyuki Inui2Hanako Nishimoto3Takashi Kurosawa4Kohei Yamaura5Tomoya Yoshikawa6Ryosuke Kuroda7Department of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineAbstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.https://doi.org/10.1186/s12891-021-04398-zHigh glucoseOxidative stressDehydroepiandrosteroneNADPH oxidaseDiabetic tendinopathy |
spellingShingle | Shintaro Mukohara Yutaka Mifune Atsuyuki Inui Hanako Nishimoto Takashi Kurosawa Kohei Yamaura Tomoya Yoshikawa Ryosuke Kuroda In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress BMC Musculoskeletal Disorders High glucose Oxidative stress Dehydroepiandrosterone NADPH oxidase Diabetic tendinopathy |
title | In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress |
title_full | In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress |
title_fullStr | In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress |
title_full_unstemmed | In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress |
title_short | In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress |
title_sort | in vitro and in vivo tenocyte protective effectiveness of dehydroepiandrosterone against high glucose induced oxidative stress |
topic | High glucose Oxidative stress Dehydroepiandrosterone NADPH oxidase Diabetic tendinopathy |
url | https://doi.org/10.1186/s12891-021-04398-z |
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