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

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/m(2)). 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.