表观遗传机制控制人工膝关节置换术后运动疗法前后的基因激活。

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

机构信息

Department of Health Science, Kansai Medical University, Osaka, Japan.

Department of Orthopaedic Surgery, Kansai Medical University Hospital, Osaka, Japan.

出版信息

Clin Interv Aging. 2019 Aug 7;14:1433-1443. doi: 10.2147/CIA.S213154. eCollection 2019.

DOI:10.2147/CIA.S213154

PMID:31496670

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6689537/

Abstract

PURPOSE

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 () 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/m). 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 (=0.046), total weight (=0.027), and total fat mass (=0.028) were significantly lower 5 months postoperatively than preoperatively. Five months post-surgery, the gene was significantly more hypomethylated at eight sites in the CpG island, compared to pre-surgery. There was a significant correlation (r=0.88, =0.02) between promoter region hypomethylation and weight loss. Total methylation rate and weight loss were significantly correlated (r=0.829, =0.042). Total methylation rate and decrease in total fat mass showed a positive trending relationship (r=0.812, =0.05).

CONCLUSION

Rehabilitative exercise resulted in significant decreases in weight and body fat. Hypomethylation of the gene promoter region signified the effect of postoperative management focus on exercise therapy on weight and fat loss.

摘要

目的

DNA 甲基化被认为在运动引起的基因表达中起作用。我们旨在研究终末期膝骨关节炎老年患者在人工膝关节置换术和运动疗法前后肌肉力量和身体成分的变化。我们旨在通过调节骨骼肌和脂肪代谢的丙酮酸脱氢酶激酶 4（）基因的甲基化率来证实 DNA 甲基化与身体成分之间的关系。

患者和方法

2017 年 4 月至 6 月期间，患者在关西医科大学医院接受人工膝关节置换术。有 6 名患者（7 个膝关节）纳入分析（4 名男性/2 名女性；平均年龄 75.7 岁；体重指数 25.1kg/m）。手术前和手术后 5 个月测量身体成分和膝关节伸肌力量。手术后进行 3 个月的康复治疗。在剩下的 2 个月中，患者使用测功计每周进行两次 20 分钟的阻力训练和有氧运动。手术期间和手术后 5 个月取股直肌活检。从活检样本中提取 DNA 后，用亚硫酸氢盐处理，计算 DNA 甲基化率。

结果

体重（=0.046）、总重量（=0.027）和总脂肪量（=0.028）术后 5 个月明显低于术前。与术前相比，术后 5 个月时，基因在 CpG 岛的 8 个位点明显去甲基化。启动子区域去甲基化与体重减轻呈显著相关（r=0.88，=0.02）。总甲基化率与体重减轻呈显著相关（r=0.829，=0.042）。总甲基化率与总脂肪量减少呈正相关趋势（r=0.812，=0.05）。