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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Main Authors: Shintaro Mukohara, Yutaka Mifune, Atsuyuki Inui, Hanako Nishimoto, Takashi Kurosawa, Kohei Yamaura, Tomoya Yoshikawa, Ryosuke Kuroda
Format: Article
Language:English
Published: BMC 2021-06-01
Series:BMC Musculoskeletal Disorders
Subjects:
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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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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