Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty

Abstract Background Although exercise is a standard treatment for postoperative osteoarthritis, interindividual differences have been reported. Epigenetic modification (DNA methylation), a factor causing interindividual differences, is altered by the environment and may affect all tissues. Performin...

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Main Authors: Tomohiro Kamo, Satoshi Kurose, Hiroshi Ohno, Minoru Murata, Takanori Saito, Yutaka Kimura
Format: Article
Language:English
Published: BMC 2020-03-01
Series:Journal of Physiological Anthropology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40101-020-00216-y
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author Tomohiro Kamo
Satoshi Kurose
Hiroshi Ohno
Minoru Murata
Takanori Saito
Yutaka Kimura
author_facet Tomohiro Kamo
Satoshi Kurose
Hiroshi Ohno
Minoru Murata
Takanori Saito
Yutaka Kimura
author_sort Tomohiro Kamo
collection DOAJ
description Abstract Background Although exercise is a standard treatment for postoperative osteoarthritis, interindividual differences have been reported. Epigenetic modification (DNA methylation), a factor causing interindividual differences, is altered by the environment and may affect all tissues. Performing a tissue biopsy to investigate methylation of skeletal muscle fat metabolism genes is invasive, and less invasive and convenient alternatives such as blood testing are desired. However, the relationship between tissue and blood is still unclear. Here, we examined the relationship between DNA methylation of the PDK4 gene in skeletal muscle and peripheral blood. Patients and methods Five patients who underwent artificial knee arthroplasty between April 2017 and June 2018 at Kansai Medical University Hospital were included (2 men and 3 women; average age, 75.2 years; body mass index, 26.1 kg/m2). We measured the body composition of the patients using dual-energy X-ray absorptiometry. Peripheral blood was collected at the time of hospitalization and 5 months after surgery; skeletal muscles were collected at the time of surgery and 5 months after surgery. Rehabilitation was performed according to the clinical procedure for 3 months after surgery. Patients performed resistance training and aerobic exercise using an ergometer for 20 min twice a week. Biopsy samples were treated with bisulfite after DNA extraction, and the methylation rate was calculated at different CpG islands downstream from the transcription initiation codon of the PDK4 gene. Results No significant change in body composition was observed before and after postoperative exercise therapy, and no significant change was noted in the methylation at each position in the promoter region of PDK4 in the skeletal muscle and peripheral blood. However, changes in the methylation rate at CpG1 in peripheral blood significantly correlated with those in skeletal muscle (P = 0.037). Furthermore, the amount of change in the methylation rate of CpG1 in the skeletal muscle was significantly correlated (P = 0.037) with the average methylation rate at the promoter region in peripheral blood. Conclusions Methylation rates at CpG1 in the skeletal muscle and peripheral blood were significantly correlated, suggesting that skeletal muscle methylation could be analyzed via peripheral blood rather than skeletal muscle biopsy.
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spelling doaj.art-e39c2453e48b45fe963509630e5314612022-12-22T03:42:30ZengBMCJournal of Physiological Anthropology1880-68052020-03-013911710.1186/s40101-020-00216-yAssociation of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplastyTomohiro Kamo0Satoshi Kurose1Hiroshi Ohno2Minoru Murata3Takanori Saito4Yutaka Kimura5Department of Health Science, Kansai Medical UniversityDepartment of Health Science, Kansai Medical UniversityDepartment of Orthopaedic Surgery, Kansai Medical University HospitalDepartment of Orthopaedic Surgery, Kansai Medical University HospitalDepartment of Orthopaedic Surgery, Kansai Medical University HospitalDepartment of Health Science, Kansai Medical UniversityAbstract Background Although exercise is a standard treatment for postoperative osteoarthritis, interindividual differences have been reported. Epigenetic modification (DNA methylation), a factor causing interindividual differences, is altered by the environment and may affect all tissues. Performing a tissue biopsy to investigate methylation of skeletal muscle fat metabolism genes is invasive, and less invasive and convenient alternatives such as blood testing are desired. However, the relationship between tissue and blood is still unclear. Here, we examined the relationship between DNA methylation of the PDK4 gene in skeletal muscle and peripheral blood. Patients and methods Five patients who underwent artificial knee arthroplasty between April 2017 and June 2018 at Kansai Medical University Hospital were included (2 men and 3 women; average age, 75.2 years; body mass index, 26.1 kg/m2). We measured the body composition of the patients using dual-energy X-ray absorptiometry. Peripheral blood was collected at the time of hospitalization and 5 months after surgery; skeletal muscles were collected at the time of surgery and 5 months after surgery. Rehabilitation was performed according to the clinical procedure for 3 months after surgery. Patients performed resistance training and aerobic exercise using an ergometer for 20 min twice a week. Biopsy samples were treated with bisulfite after DNA extraction, and the methylation rate was calculated at different CpG islands downstream from the transcription initiation codon of the PDK4 gene. Results No significant change in body composition was observed before and after postoperative exercise therapy, and no significant change was noted in the methylation at each position in the promoter region of PDK4 in the skeletal muscle and peripheral blood. However, changes in the methylation rate at CpG1 in peripheral blood significantly correlated with those in skeletal muscle (P = 0.037). Furthermore, the amount of change in the methylation rate of CpG1 in the skeletal muscle was significantly correlated (P = 0.037) with the average methylation rate at the promoter region in peripheral blood. Conclusions Methylation rates at CpG1 in the skeletal muscle and peripheral blood were significantly correlated, suggesting that skeletal muscle methylation could be analyzed via peripheral blood rather than skeletal muscle biopsy.http://link.springer.com/article/10.1186/s40101-020-00216-yPDK4 geneSkeletal musclePeripheral bloodPromoter regionPyrosequencing
spellingShingle Tomohiro Kamo
Satoshi Kurose
Hiroshi Ohno
Minoru Murata
Takanori Saito
Yutaka Kimura
Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
Journal of Physiological Anthropology
PDK4 gene
Skeletal muscle
Peripheral blood
Promoter region
Pyrosequencing
title Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
title_full Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
title_fullStr Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
title_full_unstemmed Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
title_short Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
title_sort association of epigenetics of the pdk4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty
topic PDK4 gene
Skeletal muscle
Peripheral blood
Promoter region
Pyrosequencing
url http://link.springer.com/article/10.1186/s40101-020-00216-y
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