Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty

Tomohiro Kamo,1 Satoshi Kurose,1 Hiroshi Ohno,2 Minoru Murata,2 Masaki Hashiyada,3 Takanori Saito,2 Yutaka Kimura11Department of Health Science, Kansai Medical University, Osaka, Japan; 2Department of Orthopaedic Surgery, Kansai Medical University Hospital, Osaka, Japan; 3Department of Forensic Medi...

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Autores principales: Kamo T, Kurose S, Ohno H, Murata M, Hashiyada M, Saito T, Kimura Y
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:d873f16fce3a4941a5c5ac8b01888f972021-12-02T03:06:45ZEpigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty1178-1998https://doaj.org/article/d873f16fce3a4941a5c5ac8b01888f972019-08-01T00:00:00Zhttps://www.dovepress.com/epigenetic-mechanism-controls-pdk4-gene-activation-before-and-after-ex-peer-reviewed-article-CIAhttps://doaj.org/toc/1178-1998Tomohiro Kamo,1 Satoshi Kurose,1 Hiroshi Ohno,2 Minoru Murata,2 Masaki Hashiyada,3 Takanori Saito,2 Yutaka Kimura11Department of Health Science, Kansai Medical University, Osaka, Japan; 2Department of Orthopaedic Surgery, Kansai Medical University Hospital, Osaka, Japan; 3Department of Forensic Medicine, Kansai Medical University, Osaka, JapanPurpose: DNA methylation is thought to play a role in exercise-induced gene expression. We aimed to examine changes in muscular strength and body composition in elderly patients with end-stage knee osteoarthritis before and after artificial knee arthroplasty and exercise therapy. We aimed to confirm the relationship between DNA methylation and body composition, using the methylation rate of the pyruvate dehydrogenase kinase 4 (PDK4) gene that regulates skeletal muscle and fat metabolism.Patients and methods: Patients underwent artificial knee arthroplasty between April 2017 and June 2017 at Kansai Medical University Hospital. Six patients (seven knees) were included in the analysis (four males/two females; average age, 75.7 years; body mass index, 25.1 kg/m2). Body composition and knee extension muscle strength were measured before surgery and 5 months after surgery. Rehabilitation was performed for 3 months after surgery. In the remaining 2 months, patients performed resistance training and aerobic exercise using an ergometer for 20 mins, twice a week. A biopsy of the vastus medialis was taken during surgery and 5 months post-surgery. Biopsy samples were treated with bisulfite after DNA extraction, and DNA methylation rate was calculated.Results: Body weight (P=0.046), total weight (P=0.027), and total fat mass (P=0.028) were significantly lower 5 months postoperatively than preoperatively. Five months post-surgery, the PDK4 gene was significantly more hypomethylated at eight sites in the CpG island, compared to pre-surgery. There was a significant correlation (r=0.88, P=0.02) between promoter region hypomethylation and weight loss. Total methylation rate and weight loss were significantly correlated (r=0.829, P=0.042). Total methylation rate and decrease in total fat mass showed a positive trending relationship (r=0.812, P=0.05).Conclusion: Rehabilitative exercise resulted in significant decreases in weight and body fat. Hypomethylation of the PDK4 gene promoter region signified the effect of postoperative management focus on exercise therapy on weight and fat loss.Keywords: rehabilitation, elderly person, muscle biopsy, methylationKamo TKurose SOhno HMurata MHashiyada MSaito TKimura YDove Medical Pressarticlerehabilitationelderly personmuscle biopsymethylationGeriatricsRC952-954.6ENClinical Interventions in Aging, Vol Volume 14, Pp 1433-1443 (2019)
institution DOAJ
collection DOAJ
language EN
topic rehabilitation
elderly person
muscle biopsy
methylation
Geriatrics
RC952-954.6
spellingShingle rehabilitation
elderly person
muscle biopsy
methylation
Geriatrics
RC952-954.6
Kamo T
Kurose S
Ohno H
Murata M
Hashiyada M
Saito T
Kimura Y
Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty
description Tomohiro Kamo,1 Satoshi Kurose,1 Hiroshi Ohno,2 Minoru Murata,2 Masaki Hashiyada,3 Takanori Saito,2 Yutaka Kimura11Department of Health Science, Kansai Medical University, Osaka, Japan; 2Department of Orthopaedic Surgery, Kansai Medical University Hospital, Osaka, Japan; 3Department of Forensic Medicine, Kansai Medical University, Osaka, JapanPurpose: DNA methylation is thought to play a role in exercise-induced gene expression. We aimed to examine changes in muscular strength and body composition in elderly patients with end-stage knee osteoarthritis before and after artificial knee arthroplasty and exercise therapy. We aimed to confirm the relationship between DNA methylation and body composition, using the methylation rate of the pyruvate dehydrogenase kinase 4 (PDK4) gene that regulates skeletal muscle and fat metabolism.Patients and methods: Patients underwent artificial knee arthroplasty between April 2017 and June 2017 at Kansai Medical University Hospital. Six patients (seven knees) were included in the analysis (four males/two females; average age, 75.7 years; body mass index, 25.1 kg/m2). Body composition and knee extension muscle strength were measured before surgery and 5 months after surgery. Rehabilitation was performed for 3 months after surgery. In the remaining 2 months, patients performed resistance training and aerobic exercise using an ergometer for 20 mins, twice a week. A biopsy of the vastus medialis was taken during surgery and 5 months post-surgery. Biopsy samples were treated with bisulfite after DNA extraction, and DNA methylation rate was calculated.Results: Body weight (P=0.046), total weight (P=0.027), and total fat mass (P=0.028) were significantly lower 5 months postoperatively than preoperatively. Five months post-surgery, the PDK4 gene was significantly more hypomethylated at eight sites in the CpG island, compared to pre-surgery. There was a significant correlation (r=0.88, P=0.02) between promoter region hypomethylation and weight loss. Total methylation rate and weight loss were significantly correlated (r=0.829, P=0.042). Total methylation rate and decrease in total fat mass showed a positive trending relationship (r=0.812, P=0.05).Conclusion: Rehabilitative exercise resulted in significant decreases in weight and body fat. Hypomethylation of the PDK4 gene promoter region signified the effect of postoperative management focus on exercise therapy on weight and fat loss.Keywords: rehabilitation, elderly person, muscle biopsy, methylation
format article
author Kamo T
Kurose S
Ohno H
Murata M
Hashiyada M
Saito T
Kimura Y
author_facet Kamo T
Kurose S
Ohno H
Murata M
Hashiyada M
Saito T
Kimura Y
author_sort Kamo T
title Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty
title_short Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty
title_full Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty
title_fullStr Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty
title_full_unstemmed Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty
title_sort epigenetic mechanism controls pdk4 gene activation before and after exercise therapy following artificial knee arthroplasty
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/d873f16fce3a4941a5c5ac8b01888f97
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