Submitted on April 4, 2006
Accepted on March 2, 2007
Electroacupuncture Suppresses Myostatin Gene Expression: Cell Proliferative Reaction in Mouse Skeletal Muscle
Yutaka Takaoka1*, Mika Ohta2, Akihiko Ito3, Kunihiko Takamatsu4, Aki Sugano2, Kotaro Funakoshi5, Nobuo Takaoka6, Nobuko Sato7, Hiroshi Yokozaki3, Naoki Arizono8, Shuji Goto4, and Eiichi Maeda9
1 Laboratory for Applied Genome Science, Clinical Genome Informatics Center, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Biochemistry, Iwate Medical University School of Dentistry, Morioka, Japan
2 Laboratory for Applied Genome Science, Clinical Genome Informatics Center, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Acupuncture Informatics, Goto College of Medical Arts and Sciences, Tokyo, Japan
3 Division of Surgical Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
4 Department of Acupuncture Informatics, Goto College of Medical Arts and Sciences, Tokyo, Japan
5 Laboratory for Applied Genome Science, Clinical Genome Informatics Center, Kobe University Graduate School of Medicine, Kobe, Japan
6 Faculty of Sciences, Kyushu University, Fukuoka, Japan
7 Department of Biochemistry, Iwate Medical University School of Dentistry, Morioka, Japan
8 Department of Medical Zoology, Kyoto Prefectural University of Medicine, Kobe, Japan
9 Clinical Genome Informatics Center, Kobe University Graduate School of Medicine, Kobe, Japan
* To whom correspondence should be addressed. E-mail: ytakaoka{at}med.kobe-u.ac.jp.
Complementary and alternative medicine (CAM) may provide patients with an alternative to traditional medicine, but an assessment of its efficacy is required. One CAM method, electroacupuncture (EA) treatment, is a maneuver that utilizes stimulation of acupuncture needles with a low-frequency microcurrent. To study the effect of short-term EA, we evaluated the differential expression of genes induced by EA in mouse skeletal muscle for up to 24 hours. We then used RT-PCR to confirm the expression patterns of six differentially expressed genes. Bioinformatics analysis of their transcription control regions showed that EA-inducible genes have numerous common binding motifs that are related to cell differentiation, cell proliferation, muscle repair, and hyperplasia. These results suggested that EA treatment may induce cell proliferation in skeletal muscle. To verify this possibility, we used EA to stimulate mouse skeletal muscle daily for up to 1 month and examined the long-term effects. Immunohistochemical analysis showed that nuclei of muscle cells treated with EA for 1 month, especially nuclei of satellite cells, reacted with anti-human PCNA. Also, expression of the gene encoding myostatin, which is a growth repressor in muscle satellite cells, was suppressed by daily EA treatment for 1 week; EA treatment for 1 month resulted in more marked suppression of the gene. These molecular findings constitute strong evidence that EA treatment suppresses myostatin expression, which leads to a satellite cell-related proliferative reaction and repair in skeletal muscle.
