Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Jiayu Yao,1 Xiaotong Liu,1 Yingxu Sun,1 Xin Dong,1 Li Liu,1 Hailun Gu2 1Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Department of Orthopedics, Shengjing Hospital, China Medical University, Sheny...

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Autores principales:	Yao J, Liu X, Sun Y, Dong X, Liu L, Gu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	curcumin osteoarthritis apoptosis autophagy microrna-34a high-fat diet Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b3f55972ddda4659962ac57c73178bc6
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spelling	oai:doaj.org-article:b3f55972ddda4659962ac57c73178bc62021-12-02T15:50:41ZCurcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a1178-7031https://doaj.org/article/b3f55972ddda4659962ac57c73178bc62021-06-01T00:00:00Zhttps://www.dovepress.com/curcumin-alleviated-osteoarthritic-progression-in-rats-fed-a-high-fat--peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Jiayu Yao,1 Xiaotong Liu,1 Yingxu Sun,1 Xin Dong,1 Li Liu,1 Hailun Gu2 1Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Hailun GuDepartment of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaTel +86-18940257206Email guhailun_@163.comPurpose: The mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a).Methods: Male Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis.Results: We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group.Conclusion: Curcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.Keywords: curcumin, osteoarthritis, apoptosis, autophagy, microRNA-34a, high-fat dietYao JLiu XSun YDong XLiu LGu HDove Medical Pressarticlecurcuminosteoarthritisapoptosisautophagymicrorna-34ahigh-fat dietPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2317-2331 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	curcumin osteoarthritis apoptosis autophagy microrna-34a high-fat diet Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	curcumin osteoarthritis apoptosis autophagy microrna-34a high-fat diet Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Yao J Liu X Sun Y Dong X Liu L Gu H Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a
description	Jiayu Yao,1 Xiaotong Liu,1 Yingxu Sun,1 Xin Dong,1 Li Liu,1 Hailun Gu2 1Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Hailun GuDepartment of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaTel +86-18940257206Email guhailun_@163.comPurpose: The mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a).Methods: Male Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis.Results: We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group.Conclusion: Curcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.Keywords: curcumin, osteoarthritis, apoptosis, autophagy, microRNA-34a, high-fat diet
format	article
author	Yao J Liu X Sun Y Dong X Liu L Gu H
author_facet	Yao J Liu X Sun Y Dong X Liu L Gu H
author_sort	Yao J
title	Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a
title_short	Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a
title_full	Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a
title_fullStr	Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a
title_full_unstemmed	Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a
title_sort	curcumin-alleviated osteoarthritic progression in rats fed a high-fat diet by inhibiting apoptosis and activating autophagy via modulation of microrna-34a
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b3f55972ddda4659962ac57c73178bc6
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Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

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